14th International Symposium on Marine Natural Products

Transcription

Cubierta 4:Abstracts 01/08/13 20:01 Página 1
on Marine
Natural
Products
on Marine Natural Products
14th International Symposium
8th European Conference
September 15th - 20th, 2013
La Toja Island, Galicia
Organized by:
Spain
Posters Session 2
Participants index
Interior POSTERS 2:Abstracts 02/08/13 11:31 Página 164
Tuesday 17th September, 2013
Posters Session 2
P 101
Posters Session 2
SYNTHESIS OF ISO-CLADOSPOLIDE B AND 11-EPI-ISO-CLADOSPOLIDE B
Marcos Lois Rivadulla, María Gonzalez, Andrea Martínez, Generosa Gómez,
Yagamare Fall
Universidad de Vigo, 36310, Vigo, Spain.
E-mail: [email protected]
The cladospolides (A-D) are a family of 12-membered lactones isolated from the
fermented broth of cultures derived either from marine fungi or from soil fungus.1
Unlike their macrolactones congeners, iso-cladospolide B and 11-epi-iso-cladospolide B
have a butenolide moiety in their structures and were isolated from Red sea sponge
Cladosporium sp. and also from fermentation of the marine fungal species 196S215.2
In this communication, we report a new synthesis of iso-cladospolide B and 11-epi-isocladospolide B from L-malic acid.3 This commercially available reagent, was previously
by us for the synthesis of biologically interesting natural products.4
References
1.
Posters Session 2
2.
3.
4.
Cameron, J. S.; Abbanat, D.; Bernan, V. S.; Maiese, W. M.; Greenstein, M.; Jompa, J.; Tahir, A.;
Ireland, C. M. J. Nat. Prod. 2000, 63, 142.
Gesner, S.; Cohen, N.; Ilan, M.; Yarden, O.; Carmeli, S. J. Nat. Prod. 2005, 68, 1350.
González, M.; et al. Tetrahedron Lett. (2013), http://dx.doi.org/10.1016/j.tetlet.2013.04.124
Álvarez, C.; Pérez, M.; Zúñiga, A.; Gómez, G.; Fall, Y. Synthesis 2010, 3883; (b) Gonzalez, M.;
Gándara, Z.; Covelo, B.; Gómez, G.; Fall, Y. Tetrahedron Lett. 2011, 52, 5983.
166
14th International Symposium on Marine Natural Products / 8th European Conference on Marine Natural Products
Posters Session 2
P 102
TOWARDS
T
TO
WARDS THE
THE TO
TOTAL
TAL S
SYNTHESIS
YNTHESIS O
OF
FM
MARINE
A RI NE P
POLYKETIDE
OLYKETIDE
M
ACROLIDES
MACROLIDES
Adr
riana L
orente1,1,33, Janire
Janire L
Lamariano
a ariano1, An
am
Andrés
drééss Francesch
Francesch2, Car
Carmen
men Cu
Cuevas
evas2,
Adriana
Lorente
1,3,44
1,3,5
Fernando
Fe
rnando Albericio
Allbbericio
andd Mercedes
an
Mercedes Álvarez
Á
Állvarez
1
Institute ffor
Institute
or R
Research
esearch iin
nB
Biomedicine,
iomedicine, PC
PCB-UB,
B-UB, B
Baldiri
aldiri R
Reixac
eixac 110,
0, E
E-08028
-08028 Barcelona,
Barcelona, Spain.
Spain. 2Ph
Pharma
a rm a
Ma
vda. de
de los
los Reyes
Reyes 1,
1, E-28770
E-28770 Colmenar
Colmenar Viejo,
Viejo, Madrid,
Madrid, Spain.
Spain. 3CI
CIBER-BBN,
BER-BBN, Networking
N e tw o r k in g
Marr S
S.. A
A.,., A
Avda.
Ce
ntre oonn Bioengineering,
Bioengineering, Biomaterials
Biomaterialss aand
nd Nanomedicine,
Nanomedicine, Baldiri
Baldiri R
eixac 10,
10, 08028
08028 Barcelona,
Barcelona, Spain.
Spain.
Centre
Reixac
4
Faculty
Fa
culty ooff Ch
Chemistry,
emistry, UB, E-08028
E-08028 Barcelona,
Barcelona, Spain.
Spain. 5Fa
Faculty
culty ooff Ph
Pharmacy,
harmacy, UB, E-08028
E-08028 Barcelona,
Barcelona,
o
Spain.
Spain.
E-mail: ad
riana.lorente@
@irbbarcelona.org
E-mail:
[email protected]
Marine polyketide
polyketide macrolides
macrolides are
are
r a class
class of secondary
secondaarry metabolites
metabbolites that
thatt exhibit
exhhibit
Marine
importannt and
annd diverse
diverse biological
biological activities
activities and
and are
arre excellent
excellent candidates
canndidaates for
foor the
the
important
investigation of new
new bioactive
bioactive molecules.
molecules.1 Most
Most of them
them are
arre cytotoxic
cytotoxic compounds;
compounnds;
investigation
however
have
how
ever other
otthher interesting
interesting activities
activities such
such as
as antimicrobial
antimicrobial and
annd antibacterial,
anntibacterial, ha
avve be
bbeen
en
ffound
ound
o
aass well.2 N
Nature’s
atture’s aability
bility ttoo obt
obtain
ain tthis
his cclass
lass off ccompounds
ompounds iiss tthrough
hrough tthe
he
combinaation of large
larrge multi-functional
multi-func
u tional protein
protein complexes.
complexes.
s 3 Nevertheless,
Nevertheless, ssynthesis
ynthesis iiss
combination
iimportant
mportant
n ttoo cconfirm
onffirm the
the structural
struc
r turaal determination
determinaation aand
nd to
to obtain
obbtain enough
enough sample
sam
mple amounts
amouunts
ffor
or
o further
furt
u he
h r development.
developm
p ent. A ffamily
amily of THFcontainingg m
acrolides has
has been
been isolated
isolated
THF-containing
macrolides
recently and
annd found
foound to
to be cytotoxic
cytotoxi
o c against
against various
varrious human
hum
mann tumour
tumour cell
cell lines.
lines. As
As a
recently
simplified
simplified analogue
annalogue of these
these compounds,
com
mpounds, we
we envisioned
envisioned the
the synthesis
synthesis of a derivative
derivaative
that
thaat maintains
maintains the
the macrocyclic
macrocyclic lactone.
lactone.
Posters Session 2
Wee w
will
discuss
results
macrolactone.
W
ill di
scuss our re
sults ttowards
owar
ards tthe
he ssynthesis
ynthesis of tthe
he m
acrolactone. A cconvergent
onverggent
sstrategy
traategy based
based on the
the disconnection
disconnection from
from
r
the ester
ester and
annd the
the double
double bond divides
divides the
the
the
m
oleculle iinn ttwo
wo ffragments,
rragments, w
hich aare
r pre
re
parred iindependently.
ndependdently. O
ur ffi
irst eefforts
ffort
o s w
ere
molecule
which
prepared
Our
first
were
based
ba
sed onn ann olefin
olefin metathesis
metathesis strategy.
strat
r tegy. Finally,
Finally, a strategy
strattegyy based
based on a Julia-Kocienski
Julia-Kociens
n ki
ol
efinattion led
led to
to the
the desired
desired product.
product. Because
Becauuse two
two of the
the stereocenters
stereocenters of the
the
olefination
m
acrolactone ar
re sstill
till un
known, our eefforts
fffoorts aare
re ffocused
oc
o used oonn tthe
he ssynthesis
ynthesis of one ssingle
ingl
n e
macrolactone
are
unknown,
di
astereoiso
o mer, planning
planning the
the synthesis
synnthesis off the
the
h other
other stereoisomers
stereoisomers on a later
latter stage.
stage.
diastereoisomer,
References
R
eferences
1..
2..
3..
Lorente,
Lorente, A.;
A.; Lamariano,
Lamariano, J.;
J.; Albercio,
Albercio, F.;
F.; Álvarez,
Álvarez, M.
M. Chem.
Chem. Rev.
Rev. 2013, 10.
10.1021/cr3004778.
1021/cr3004778.
Kobayashi, J.;
J.; Ku
bota, T.
T. J.
J N
a t. P
rod. 2007, 770,
0, 451.
451. ((b)
b) Ki
goshi, H.
Hayakawa, II.. Ch
hem .
Kobayashi,
Kubota,
Nat.
Prod.
Kigoshi,
H.;; Hayakawa,
Chem.
Re
c. 2007, 77,, 2254.
54. (b)
(b) Qi,
Qi, Y.;
Y.; Ma,
Ma, S.
S. Ch
em . M
ed. Ch
em. 20
011, 66,, 3399.
99.
Rec.
Chem.
Med.
Chem.
2011,
St
aunton, J.;
J.; Weissman,
Weissman, K.
K. J.
J. Na
t. P
rod. R
ep. 2001, 18, 3380.
80. ((b)
b) Kwa
n, D. H.;
H.; Schulz,
S c h u lz , F
Staunton,
Nat.
Prod.
Rep.
Kwan,
F..
Mo
lecules 2011, 16
092.
Molecules
16,, 66092.
167
P 103
Posters Session 2
TOTAL
T
OTAL S
SYNTHESIS
YNTHESIS AND ST
STRUCTURAL
TRUCTURAL A
ASSIGNMENT
SSIGNMENT OF BARMUMYC
BARMUMYCIN
CIN
, ,
Adrian
a a Lorente
Lorente 1,3, , L
Librada
ibrada M
M.. Cañ
Cañedo
edo 2, Fe
Fernando
rnando Albericio
A
Allbbericio1,3,4
and
and Mercedes
Mercedes
Adriana
1,3,4
Állvarez
Álvarez
1
Institute ffor
Institute
or R
Research
esearch iin
nB
Biomedicine,
io m e d ic in e , B
Barcelona
arcelona S
Science
cience Park,
Park, University
University of
of Barcelona,
Barcelona, Baldiri
Baldiri Reixac
R e ix a c
08028 Barcelona,
Barcelona, Spain,
Spain, 2 In
Instituto
s titu to B
Biomar,
iomar, S.A.
S.A. Parque
Parque Tecnològico
Tecnològico de León-M10.4,
León-M10.4, E
E-24009
-240009
10, E-0
E-08028
Ar
munia, León,
León, Spain
Spain ,3CI
CIBER-BBN,
BER-BB
BN, Networking
Networking Centre
Centre on
on Bioengineering,
Bioengineering, Biomaterials
Biomaterials and
and
Armunia,
Nanomedicine,
Barcelona
Baldiri
Reixac
Nanomedicine, Ba
rcelona Science
Science Park,
Park, Ba
ldiri Re
ixac 10,
10, 008028
8028 Barcelona,
B rcelona, Spain
Ba
Spain 4 Department
Department of
of
Or
ganic Chemistry,
Chemistry, Faculty
Faculty of
of Chemistry,
Chemistry, University
University ooff B
arcelona, 008028
8028 Barcelona,
Barcelona, Spain,
Spain, and
and
Organic
Barcelona,
e
Laboratory
La
boratory ooff Organic
Organic Chemistry,
Chemistrry, Faculty
Faculty of
of Pharmacy,
Pharmacy, University
University of
of Barcelona,
Barcelona, 08028
08028 Barcelona,
B a r c e lo n a ,
Sp
a in .
Spain.
EE
mail: ad
riana.
a lorente@irbbarcelona.
a org, me
[email protected].
E-mail:
[email protected],
[email protected].
Barmum
mycin1 was
was isolated
isolatted from
from
r
an
an extract
extract of the
thhe marine
marrine actinomycete
actinom
myycete St
Streptomyces
repptom
myces ssp.
p.
Barmumycin
BOSC-022A
to
BO
SC-0022A and
and
n found
found
o
to be cytotoxic
cyttotoxic against
against various
vaarrious human
huuman tumor
tumor cell
cell lines.
lines. On
On the
the
ba
sis off preliminary
preliminaarry one
nd ttwo-dimensional
wo-dimensional 1H and
annd 133C NMR
NMR spectra,
spectra, the
the natural
nattural
basis
one-- an
and
compound
compouund was
was initially
initially assigned
assigned the
the structure
structure of macrolactone-type
macrolactone-type compound
compound 1,
1, which
whi
h ch
was
differences
was prepared
preeparred by two
two different
differentt routes.
routes. However,
However, major
major
o spectroscopic
spectroscopic di
fferenc
n es
between isolated
isolatted barmumycin
barrmumycin and
and 1 led
led to
to revision
revision of the
thhe proposed
proposed structure
structure
u as
as 2. The
The
between
new
new proposed
prooposed structure
structure should
should have
havve similar
ha
similarr predicted
predicted chemical
che
h mical shifts,
shifts, and
annd the
the main
main
difference
differenc
n e between
between the
the former
foormer and
and the
an
the latter
latter should
should be the
the connectivity
connectivity between
between the
the
aromatic
arromattic ssystem
ystem and
and the
the alkyl
alkyl chain.
cha
h in. On
On the
the basis
basis of the
the enantioselective
enaanntioselective synthesis
synthesis of
this
this new
new compound,
compound, and
and subsequent
subseque
q nt spectroscopic
spectroscopic comparison
compa
parrison of it
it to
to an
an authentic
auutheentic
sample
sample of barmumycin,
barrmumycin, the
the
h structure
structure of the
the natural
naatural compound
compouund was
was indeed
indeed confirmed
conffirmed as
as
that
results
will
discussed
well
thaat of 2. Our
Our synthetic
synthetic re
sults w
ill be di
scussed aass w
ell aass tthe
he ccomparison
om
mpparison of bot
bboth
th
structures.
structurees.
Posters Session 2
R
eferences
References
1.
168
L rente, A.;
Lo
A.; Pla,
Pla, D.;
D.; Cañedo,
Cañedo, L.
L. M.;
M .; A
lbericio, F.;
F.; Álvarez,
Álvarez, M.
M. J.
J O
rg . C
hem., 2010,
2010 75,
75, 88508.
508.
Lorente,
Albericio,
Org.
Chem.,
Posters Session 2
P 104
STEREOCONTROLLED TOTAL SYNTHESIS AND STRUCTURAL
REVISION OF CRISTATUMIN D
Paula Lorenzo, Rosana Álvarez, Ángel Rodríguez de Lera
University of Vigo, Lagoas-Marcosende, 36310, Vigo, Spain.
Posters Session 2
Marine microorganisms, especially marine fungi, are known to be rich sources of
structurally interesting and biologically active compounds. The fungal genus Eurotium,
which is the teleomorph of Aspergillus, has been proved to contain an important class of
secondary metabolites with structure of tryptophan-derived alkaloids.1 Recently, from
the endophytic fungus Eurotium cristatum EN-220, extracted from the marine alga
Sargassum thunbergii, a new indole alkaloid called cristatumin D (1) was isolated,
which showed moderate antimicrobial and antifungal activities.2 Cristatumin D is a
heterodimeric diketopiperazine alkaloid that consists of two subunits of a
hexahydropyrrolo[2,3-b]indole fused to a diketopiperazine ring. Both subunits are
connected to each other through the C3 and C3’ atoms, forming a characteristic
arrangement of two contiguous quaternary stereogenic centers with the same
configuration.
Based on our experience in these type of compounds,3 we have carried out a
stereoselective total synthesis of cristatumin D based on two key disconnections: i) the
construction of the diketopiperazine rings in the last stage, by simple condensation
between the methyl esters and the corresponding L-alanine or D-valine and, ii) the
formation of dimeric hexahydropyrrolo[2,3-b]indole by reductive dimerization mediated
by CoCl(PPh3)3. The analysis of their spectroscopic data of the synthetic material was
inconsistent with those of the natural product (2) and the structure was revised. This
revision is yet another example of the fundamental role of total synthesis in the
validation of the proposed structures of natural products.4
References
1
2
3
4
(a) Slack, G. J.; Puniani, E.; Frisvad, J. C.; Samson, R. A.; Miller, J. D. Mycol. Res. 2009, 113,
480 (b) Li, D. L.; Li, X. M.; Wang, B. G. J. Microbiol. Biotechnol. 2009, 19, 675. 2.
Du, F. Y.; Li, X. M.; Li, C. S.; Shang, Z.; Wang, B. G. Bioorg. Med. Chem. Lett. 2012, 22, 4650.
3.
(a) Silva, C.; Pérez-Balado, C.; Rodríguez, P.; de Lera, A. R. Org. Lett. 2008, 10, 77. (b) PérezBalado, C.; de Lera, A. R. Org. Lett. 2008, 10, 3701.
Pérez-Balado, C.; Rodríguez, P.; de Lera, A. R. Chem. Eur. J. 2009, 15, 9928. 4. Nicolaou, K.
C.; Snyder, S. A. Angew. Chem. Int. Ed. 2005, 44, 1012.
Acknowledgements.
We thank the Spanish Ministerio de Educación y Ciencia (Grant SAF2010-17935-FEDER) for financial
support.
169
P 105
Posters Session 2
INFLUENCE OF NATURAL SUBSTRATES AND CO-OCCURRING MARINE
BACTERIA ON THE PRODUCTION OF SECONDARY METABOLITES BY
Photobacterium halotolerans
Maria Månsson1, Kirsten A. Moeller1, Sonia Giobergia2, Pieter Dorrestein3, and Lone
Gram1
1
Department of Systems Biology, Technical University of Denmark. 2The Novo Nordisk Foundation Center
forBiosustainability, Technical University of Denmark. 3Skaggs School of Pharmacy and Pharmaceutical
Sciences, Departments of Pharmacology, Chemistry and Biochemistry, University of California San Diego
E-mail:[email protected]
Genome sequences reveal that our current standard laboratory conditions only support a
fraction of the potential secondary metabolism in bacteria. Thus, we must rethink
cultivation, detection, and isolation strategies for bacterial secondary metabolites in order to
explore the so far uncharacterized chemical potential of these organisms.We are currently
investigating the use of natural substrates and co-cultures with commensal bacteria to elicit
or alter production of antibacterial compounds in marine bacteria. One of our target
organisms isPhotobacterium halotolerans, a marine Vibrionaceae bacterium that produces
a series of bioactive compounds, including the antibiotic holomycin1 and the solonamides
that attenuate virulence in Staphyloccocus aureus.2 We found the production of these
compounds were largely unaffected by changes in media or presence of other bacteria;
however, using MALDI-TOF imaging mass spectrometry3 we found another group of
metabolites, the ngercheumicins4to be strongly induced by presence of other bacteria. In
addition, we have used molecular networking5 of live (with nanoDESI) and extracted
bacterial colonies to identify changes in metabolite production on complex and natural
substrates. Growth of P. halotolerans on chitin, an N-acetyl-D-glucosamine polymer found
in the exoskeleton of zooplankton, resulted in the production of potential novel metabolites
not observed on standard glucose-based media. Our results support the hypothesis that
rational use of substrates and co-cultures that mimic natural conditions represents a fruitful
approach for elicitation of natural product production in marine bacteria.
References
1.
2.
Posters Session 2
3.
4.
5.
170
Wietz, M.; Mansson, M.; Gotfredsen, C. H.; Larsen, T. O.; Gram, L. Marine drugs2010, 8, 2946–60.
Mansson, M.; Nielsen, A.; Kjærulff, L.; Gotfredsen, C. H.; Wietz, M.; Ingmer, H.; Gram, L.; Larsen,
T. O. Marine drugs2011, 9, 2537–52.
Yang, J. Y.; Phelan, V. V; Simkovsky, R.; Watrous, J. D.; Trial, R. M.; Fleming, T. C.; Wenter, R.;
Moore, B. S.; Golden, S. S.; Pogliano, K.; Dorrestein, P. C. Journal of bacteriology2012, 194, 6023–
8.
Kjærulff, L; Mansson, M.; Gram, L.; Larsen, T.O.; Gotfredsen, C.H.To be submitted 2013.
Watrous, J.; Roach, P.; Alexandrov, T.; Heath, B. S.; Yang, J. Y.; Kersten, R. D.; Van der Voort, M.;
Pogliano, K.; Gross, H.; Raaijmakers, J. M.; Moore, B. S.; Laskin, J.; Bandeira, N.; Dorrestein, P. C.
Proceedings of the National Academy of Sciences of the United States of America2012, 109, E1743–
52.
Posters Session 2
P 106
UTILISATION OF METABOLOMICS TO STUDY THE PRODUCTION OF
SECONDARY METABOLITES IN BACTERIAL ENDOSYMBIONTS
ISOLATED FROM MARINE SPONGES FOUND IN SCOTTISH COASTAL
WATERS
Lynsey Macintyre1, Tong Zhang1, Catherine Dowdells1, Ignacio Martinez1, Carol
Clements2, Louise Young2, Ute Hentschel-Humeida3, Christine Gernert3, Cheng
Cheng3, Ruangelie Edrada-Ebel1
1
University of Strathclyde, Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral
Street, Glasgow, G4 0re, Glasgow, United Kingdom. 2Strathclyde Innovations in Drug Research
(S.I.D.R), University of Strathclyde, Glasgow, G4 0re, United Kingdom. 3University of Würzburg, JuliusVon-Sachs Institute for Biological Sciences, Julius-Von-Sachs-Platz 3, Würzburg, 97082, Germany.
Email: [email protected]
Posters Session 2
SeaBioTech is an EU-FP7 project designed and driven by SMEs to create innovative
marine biodiscovery pipelines as a means to convert the potential of marine
biotechnology into novel industrial products for the pharmaceutical, cosmetic,
functional food and industrial chemistry sectors. Sponges are a rich source of novel
metabolites that are of medicinal interest particularly as anticancer compounds. Spongeassociated endosymbiotic bacteria produce a plethora of novel secondary metabolites
which may be structurally unique with interesting pharmacological properties. They
provide chemical defence against environmental stresses such as predators and
overgrowth of fouling organisms. Some of these secondary metabolites can be produced
in large quantities on a biotechnological scale without the need to harvest the sponge
and are therefore an economically viable source of commercial quantities of metabolites
of interest.
The metabolomic methods of dereplication and metabolic profiling were used to
identify pharmacologically relevant secondary metabolites from 80 sponge-associated
endosymbiotic bacteria using LC-FTMS and NMR spectroscopy to analyse microbial
extracts from solid cultures and liquid broths. Following taxonomic identification and
bioassay screening, multivariate statistical analysis methods were employed for
bioactive compound discovery. Several species of Vibrionaceae were identified that
displayed strong anti-mycobacterial activity against Mycobacterium marinum.
Differences in the mass spectrometry and NMR spectra from active and inactive
bacterial extracts were probed using multivariate analysis in an attempt to uncover
metabolites responsible for the bioactivity during the dereplication process. This study
illustrates how metabolomics can be utilised to accelerate the selection of
endosymbionts to take forward to scale-up, potentially fast-tracking the drug discovery
process.
171
P 107
Posters Session 2
A NEWANTIBACTERIAL POLYKETIDE FROM THE MARINE ALGADERIVED ENDOPHITIC Streptomyces sundarbansensis WR1L1S8
Ines Mancini1, IbtissemDjinni1,2, Andrea Defant1 and MouloudKecha 2
1
Bioorganic Chemistry Laboratory, Department of Physics, University of Trento, via Sommarive 1438123 Povo Trento- Italy. 2Laboratory of Applied Microbiology, Faculty of Nature Science and Life,
University of Bejaia, TargaOuzemmour,Bejaia 06000, Algeria
Posters Session 2
With the aim of finding novel marine actinobacteria strains able to produce bioactive
metabolites, twenty two algae-derived actinomycetales were isolated in Bejaia coastline,
Algeria. The crude EtOAc extract from Streptomyces sp. WR1L1S8, obtained from
brown algae Fucus sp. and identified as Streptomyces sundarbansensis by 16S rRNA
analysis, showed the most promising inhibition on the growth of a series of Gram
positive and Gram negative bacteria.
The known phaechromicin B, C and E were isolated,1 together with the new
chiral polyketide 1, bearing an unusual propyl chain. The 2-hydroxy- -pyrone form was
established based on the comparison of the experimental FT-IR spectrum to the DFT
calculated spectra for both the 2-hydroxy- -pyrone and 4-hydroxy--pyrone forms and
to standard compounds.Metabolite 1 stood out as the most active among the products
isolated from Streptomyces sp. WR1L1S8, showing a selective activity against
thepathogenic methicillin-resistant S. aureus (MRSA), with a MIC value = 6 μ.2
A further study was designed in order to investigate whether culture conditions
(media, seawater concentration and pH values), could induce S. sundarbansensis to
produce compound 1. It resulted the major metabolite from starch casein agar (SCA)
medium in 50% seawater at pH 7. Metabolite profiles obtained under different culture
condition were efficiently evaluated through the analysis on the corresponding crude
extracts by online HPLC-DAD/ESI-MS technique.3
References
1.
2.
3.
172
Graziani, E.I., Ritacco, F.V., Bernan, V.S., Telliez, J.B. J. Nat. Prod. 2005, 68, 1262.
Djinni, I., Defant, A., Kecha, M., Mancini, I. Mar. Drugs, 2013, 11, 124.
Djinni, I., Defant, A., Kecha, M., Mancini, I. Res.Microbiol., in press
Posters Session 2
P 108
SYNTHETIC
S
YNTHETIC S
STRATEGIES
TR
RATEGIES
E F
FOR
OR TH
THE
EP
PREPARATION
REPARATION O
OF
F BI
BIOACTIVE
OACTIVE
G
LY
YCOGLYCEROLIPIDS
GLYCOGLYCEROLIPIDS
Emiliano M
aanzo,
o, D
Dario
ario Pagano
Paagano and
and Angelo
Ange
g lo Fontana
Fontan
a a
Emiliano
Manzo,
Institute
In
stitute ooff B
Biomolecular
io m o le c u la r C
Chemistry
hemistry (National
(National Council
Council of
of Research),
Research), via
via campi
campi flegrei
flegrei 3-80078,
3-80078, Pozzuoli,
Pozzuol
u i,
Na
ples-Italy
Naples-Italy
E
Em
ail: em
[email protected]
Email:
[email protected]
Complex
Com
plex lipids
lipids are
are
r cell membrane
membbraanne constituents
constituents and
annd are
arre present
present in
in all
all the
the living
livingg
organ
nisms. Some
Some of them
them have
haavvee also
also other
other functional
func
u tional roles
r es and
rol
annd are
are
r recognized
recognized
organisms.
1-3
-3
m
arke
r rss for
for
o the
the cellular
cellular recognition
recogni
g tion and
annd communication.
communicaattion.1Glycolipids
Glyycolippids are
arre featured
featuured
markers
by the
the presence
p sence of one or more
pre
more carbohydrates
car
arbohydraates and
annd are
arre structurally
structuurally divided
divided in
in different
different
n
fam
milies including
including glycoglycerolipids,
glycoglycerolipi
p ds, with
with acylated
acylated glycerol
glycerol
r bound to
to carbohydrate,
carrbohydratte,
families
gl
ycosphhingolipids with
with an
an acylated
acylated sphingosine
sphingosine (ceramide)
(ceraamide) and
annd isoprenoid
isoprenoid
glycosphingolipids
gl
ycoside
d s, with
with a terpene
terpene alcohol
alcohhol as
as aglycone.
aglycone. In the
the last
last years,
yearrs, members
members of the
thee
glycosides,
family,
fam
mily, especially
especially galactosyldiacylglycerols
galactosyldiacylglycerols and
annd ceramides,
ceraam
mides, have
have attracted
attracted the
thee
iinterest
nterest of the
the bio-medical
bio-medical community
community for
for
o their
thheir properties
properties in
in cancer
canncer
chemoprevention
ch
emoprevention4 aand
nd immunology.
immunology.
o 5H
Here
ere we
we discuss
discuss a versatile
versattile strategy
straategy for
for
o the
thee
synthesis of galactosyldiacylglycerols
galactosyldiacylglycerols6 an
and
nd sulphoquinovosyldiacylglycerols
sulphoquinovoosyldiacylglycerols7 whose
whose
synthesis
availability
hampered
difficulty
avvailabbility is ham
mpered by the
the di
fficulty in
in their
their isolation
isolation and
and purification
purification from
frrom
m
natural
naatural ssources.
ources.
References
R
eferences
2.
3.
4.
5.
6.
7.
Oshida,Y.,
O hida,Y., Yamada,S.,
Os
Yamada,S., Matsunaga,
Matsunaga, K.,
K., Moriya,
Moriya, T.,
T., Ohizumi,
Ohizumi, Y.,
Y., J.Nat.Prod.,
J.Nat.Prod., 1994,
1994, 557(4),
7(4), 5534345
536.
N kato,K.,Guo,C-T, Matsufuji,M.,
Na
M a ts u f u ji,M ., Y
oshimoto, A.,
A., Inagaki,
Inagaki, M.,
M., Higuchi,
Higuchi, R.,
R., Suzuki,
Suzuki, Y.,
Y., J.
Nakato,K.,Guo,C-T,
Yoshimoto,
B ochem., 2000,
Bi
2000, 1127,
27, 191-198.
191-198.
Biochem.,
M ra k a m i, C
Mu
amazaki,T., Hanashima,S.,
Hanashima,S., Takahashi,S.,
T a k a h a s h i,S ., T
Akemura,M., Yoshida,S.,
Yoshida,S., Ohta,K.,
O h ta ,K .,
Murakami,
C.,., Y
Yamazaki,T.,
TAkemura,M.,
Y shida,H., Sugawara,F.,
Yo
Sugawara,F., Sakaguchi,K.,
Sakaguchi,K., Mizushina,Y.,
Mizushina,Y., Biochim.
Biochim. Biophysica
Biophysica Acta,
Acta, 2003,
2003, 11645,
645,
Yoshida,H.,
7
72-80.
C lombo, D.,
Co
D., Scala,
Scala, A.,
A., Taiano,
Taiano, I.M.,
I.M., Toma,
Toma, L.,
L., Ro
ncheti, F.,
F., Tokuda,
Tokuda, H.,
H., Nishino,
Nishino, H.,
H .,
Colombo,
Roncheti,
S kakibara, J.,
Sa
J., Bioorg.Med.Chem.Lett,
Bioorg.Med.Chem.Lett, 1996,
1996, 66,, 11187-1190.
187-1190.
Sakakibara,
D Libero,
Libero, G.,
G., Mori,
Mori, L.
L. Nature
Nature Rev.
Rev. 2005,
2005, 5,
5, 485485- 496;
496; Di
Di libero,
libero, G.
G. Science
Science 2004, 303,
303, 4485-486.
85-4486.
Di
M nzo,E.; Ciavatta,
Ma
Ciavatta, M.L.;
M.L.; Pagano,
Pagano, D.;
D.; Fontana,
Fontana, A.
A. Tetrahedron
Tetrahedron Letters,
Letters, 2012, 53,
53, 879-881.
879-881.
Manzo,E.;
M nzo, E
Ma
E.;
.; T
Tramice,
ra m ic e , A
A.;
.; P
Pagano,
agano, D
D.;
.; Tr
Trincone,
incone, A.;
A.; Fontana,
Fontana, A. Te
Tetrahedron,
trahedron, 2012, 68, 1016910169Manzo,
10175.
1
Posters Session 2
1.
173
P 109
Posters Session 2
SOLID-PHASE
S
OLID-PHASE TO
TOTAL
TAL S
SYNTHESIS
YNTHESIS A
AND
ND F
FULL
ULL S
STRUCTURAL
TRUCTURAL
ASSIGNMENT O
FS
TELLATOLIDE A
EW M
AR INE
ASSIGNMENT
OF
STELLATOLIDE
A,, A N
NEW
MARINE
CYCLODEPSIPEPTIDE
CYCLODEPSIPEPTIDE
Mar
a ía Jesús
Jesús Martín
Mar
a tín1, Val
Valentín
lentín M
Martínez
ar
a tínez1, Car
Carmen
men Murcia
Murcia1, IIsabel
sabel D
Digón
iggón1, IIsabel
sabeel
María
1
1
1
2
Marco
M
ar
a co , An
Andrés
drés Francesch
Francesch , S
Simon
imon M
Munt
unt , Yesica
Yesica G
Garcia-Ramos
arrcia--R
Ramos , Marta
Maarta PelayPelaayy2
G
Gimeno
, Judit
Judit Tulla-Puche
Tulla--P
Puche2, Fe
Fernando
rnando Albericio
Allbbericio2 an
andd Carmen
Carmen Cuevas
Cuevas1
1
Medicinal
Me
d ic in a l C
Chemistry
h e m is try D
Department,
epartment, Ph
PharmaMar,
armaMar, S. A
A.,
., A
Avenida
venida de
de los
los Reyes,
Reyes, 1,
1, 28770
28770 - Colmenar
Colmenar Viejo,
Vie
ie jo ,
Ma
d rid , S
pain. 2In
Institute
stitute ffor
or R
Research
esearch in
in Biomedicine,
Biomedicine, Barcelona
Barcelona Science
Science Park
Park (PCB),
(PCB), Baldiri
Baldiri Reixac,
Reixac,
c 10,
10,
Madrid,
Spain.
08028 - Barcelona,
Barcelona, Spain.
S p a in .
E-ma
ail: [email protected]
[email protected]
E-mail:
Stellatolide
Stellatoolide A is
is a novel
novel cyclic
cyclic depsiundecapeptide
depsiundecappeptide and
anndd the
the most
most abundant
abbundaannt peptide
pept
p ide
isolated
a Madagascan
Ecionemia
isolated from
from
r
Madagascan sample
sampple of the
the sponge
sponge E
cioneemia acervus.
acervus. Stellatolide
Stellatolide A
contains
N-terminus,
containss a unique
unique --hydroxy
hydroxy acid
acid moiety
moiety blocking
blocking the
thee N
N-terminus, whilst
whilst the
thhe Cviaa a DD-allo-threonine
residue.
tterminus
erminuss iiss llactonized
actonized vi
alloo threonine re
sidue.
The
22-membered
macrocycle
Stellatolide
made
and
T
he 22
-membered m
acrocycle off S
tellatolide A iiss m
ade up of sseven
even ssubunits,
ubunits, an
n iiss
nd
to
cconnected
onnected tthrough
hrough ann amide
amide bond
b
to a linear
linear sidechain
sidecha
h in comprising
comprising a complex
com
mpplex
-hydroxy
Four
unusual
non-proteinogenic
-amino
ttetrapeptide
etrappept
p ide tterminated
erminated by a -hy
ydroxy aacid.
cid. F
our unus
uaal non
-proteinogenic am
mino
residues
present
molecule,
namely
aacid
cid re
esidues aare
rre pre
sent iinn tthe
he m
olecule, nam
mely --methoxytyrosine,
methoxytyrosine, 3,4dimethylglutamine,
2,3-diaminobutanoic
2,4-diamino-3-hydroxy-4di
methyylglutam
mine, 2,3
-diaminobut
n
anoi
n c aacid
cid aand
nnd 2,4diamino-3-hydroxyy-4oxobutanoic
(3-hydroxyasparagine).
oxobut
anoi
n c aacid
cid (3
-hydroxyaspaarragine).
Posters Session 2
Herein,
part
Stellatolide
and
H
erein, aass par
rt of our eefforts
ffort
o s ttoo iimprove
mprove tthe
he aavailability
vvailabi
b lity of
o S
tellatolide A an
nd eexplore
xplore
potential
wee re
report
pot
ential ccytotoxic
ytotoxic ttherapeutic
herapeutic aapplications,
ppplications, w
port aann eefficient
fficient solid-phase
solid-phase method
method
h
Stellatolide
ffor
or
o tthe
he ffirst
irst ttotal
otal ssynthesis
ynthesis of S
teellatolide A aand
nd tthe
he ffull
ul
u l sstructural
trructural assignment,
assignment, as
as well
well
moiety,
aass tthe
he aasymmetric
sym
mmetrric ssynthesis
ynthesis of the
the
h unique
unique --hydroxy
hydroxy aacid
cid m
oiety, ((Z)-3-hydroxy-6,8Z))-3-hydroxy-6,8Z
dimethylnon-4-enoic
di
methyylnon-4-enoic aacid.
cid.
174
Posters Session 2
P 110
ALKYL-TRIPHENYLPHOSPHONIUM SALTS AS MARINE ANTIFOULING
AGENTS: INHIBITION OF MICROBIAL FOULING
Alberto Jonatan Martín-Rodríguez1, José Javier Fernández Castro1, Víctor S.
Martín1, Cirilo Pérez2, Antonio Hernández Daranas1, Octavio Llinás3, Manuel Norte1
1
IUBO-AG, University of La Laguna , Av. Astrofísico Francisco Sánchez 2, 38206, La Laguna, Tenerife,
Spain. 2IUBO-AG, University of La Laguna , Spanish National Research Council (CSIC), Av. Astrofísico
Francisco Sánchez 3, 38206, La Laguna, Tenerife, Spain. 3Oceanic Platform of The Canary Islands
(PLOCAN), Carretera de Taliarte s/n, 35214, Telde, Gran Canaria, Spain.
Biofouling, the undesirable settlement and proliferation of marine organisms on manmade substrata, imposes severe economic costs to human activities in the sea.1 Since the
ban on organotin compounds in 2008, alternative antifouling compounds are needed. In
this context, quaternary phosphonium salts, which have been focus of attention in recent
years in biomedical research for their antiproliferative and antibacterial properties,2,3
arise as a promising class of molecules with a high potential for antifouling
applications. We have evaluated the bioactivity of several alkyl triphenylphosphonium
bromides differing mainly in the length of the alkyl chain towards a panel of microbial
foulers (marine bacteria, marine-derived fungi and benthic diatoms). A clear correlation
between the biological activity and the liphophilicity of the cations has been observed.
Compounds with alkyl chains of 11-13 carbons displayed the highest bioactivities, with
half-maximal inhibitory concentration (IC50) values below 5 μM for most of the test
organisms. Toxicity on Artemia salina nauplii was observed at similar concentrations.
The results reported herein indicate that covalent attachment of these molecules to
material surfaces and polymers could provide an efficient solution for the control of the
early stages of the biofouling process.
References
2.
3.
Yebra, D.M.; Kiil, S.; Dam-Johansen, K. Antifouling Technology - Past, Present and Future
Steps Towards Efficient and Environmentally Friendly Antifouling Coatings. Prog. Org.
Coatings 2004, 50, 75-104.
Millard, M.; Pathania, D.; Shabaik, Y.; Taheri, L.; Deng, J.; Neamati, N. Preclinical Evaluation
of Novel Triphenylphosphonium Salts with Broad-Spectrum Activity. PLoS One 2010, 5 (10),
e13131.
Cai, X.; Zhang, J.; Ouyang, Y.; Ma, D.; Tan, S.; Peng, Y. Bacteria-Adsorbed Palygorskite
Stabilizes the Quaternary Phosphonium Salt with Specific-Targeting Capability, Long-Term
Antibacterial Activity, and Lower Cytotoxicity. Langmuir 2013, 29, 5279-5285.
Posters Session 2
1.
Acknowledgments
This research was supported by the Spanish MINECO (projects CTQ2011-28417-C02-01/BQU and
SAF2011-28883-C03-01). A.J.M-R. acknowledges PLOCAN for the grant received.
175
P 111
Posters Session 2
NEW HECTOCHLORIN DERIVATIVES ISOLATED FROM THE
CYANOBACTERIUM Lyngbya sp. TOTAL SYNTHESIS OF
HECTOCHLORIN C ANALOGUES
Valentín Martínez1, Alfredo Rodríguez1, Fernando Reyes2, Isabel Digón1, Agustín
Gutiérrez1, Andrés Francesch1, Simon Munt1 and Carmen Cuevas1
1
Medicinal Chemistry Department, PharmaMar, S. A., Avenida de los Reyes, 1, 28770 - Colmenar Viejo,
Madrid, Spain. 2Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos
Innovadores en Andalucía. Avenida del Conocimiento 3; Edificio Centro de Desarrollo Farmacéutico y
Alimentario. Parque Tecnológico de Ciencias de la Salud. 18016 - Granada, Spain.
Hectochlorins1 and Lyngbyabellin2 are marine cyanobacterial -hydroxy-containing
lipopeptides with significant antifungal and cytotoxic activity. Hectochlorin shows a
unique cytotoxicity profile by the COMPARE algorithm, being a strong promoter of
actin polymerization.
During the study of the cyanobaterium Lyngbya sp. collected off the coast of Fiji, two
new hectochlorin analogues named Hectochlorin C and D were isolated together with
their non-cyclic analogues Hectochlorin E and F. Their structures have been elucidated
by mass spectrometry and 1D and 2D NMR experiments (1H, 13C, COSY, HSQC,
HMBC) and the stereochemistry was determined by comparing their NMR data with
that of the reported Hectochlorins.
The cytotoxic activity of Hectochlorins C-F has been tested against three human tumor
cell lines,3 lung (A549), colon (HT29) and breast (MDA-MB-231), and all the
compounds exhibited moderate cytotoxicity against the lines.
Posters Session 2
Synthetic studies have been conducted to develop a flexible route to the hectochlorin
core and to provide access to new synthetic analogues with potentially improved
activity and/or other improved attributes relative to the natural product.
References
1.
2.
3.
176
B. L. Marquez, K. S. Watts, A. Yokochi, M. A. Roberts, P. Verdier-Pinard , J. I. Jimenez, E.
Hamel, P. J. Scheuer , W. H. Gerwick. J. Nat. Prod. 2005, 68, 951.
H. Luesch, W. Y. Yoshida, R. E. Moore, V. J. Paul, S. L. Mooberry. J. Nat. Prod. 2000, 63, 611.
P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J. T. Warren, H.
Bokesch, S. Kenney, M. R. Boyd. J. Natl. Cancer Inst. 1990, 82, 1107.
Posters Session 2
P 112
AN APPROACH TO THE SYNTHESIS OF MARINE EPOXYLIPIDS
Andrea Martínez Domínguez, Maria González, Andrea Zúñiga, Generosa Gómez,
Yagamare Fall
University of Vigo, Departamento Química Orgánica; As Lagoas Marcosende, 36200, Vigo, Spain
The epoxylipids 1 and 2 (Figure 1), isolated from the Australian brown algae Notheia
anomala, are potent and selective inhibitors of the larval development of parasitic
nematodes,1 hence they have been synthetic targets for the past three decades.
We report here a formal synthesis of 1 from L-Malic acid, a cheap and commercially
available reagent, which we previously used for the synthesis of 2,5-disubstituted 3oxygenated tetrahydrofurans.2
References
Roy, S.; Spilling, C.D. Org. Lett. 2012, 14, 2230-2233.
Álvarez, C.; Pérez, M.; Zúñiga, A.; Gómez, G.; Fall, Y. Synthesis 2010, 22, 3883-3890.
Posters Session 2
1.
2.
177
P 113
Posters Session 2
THE BACTERIAL STRAIN Jeotgalicoccus halophilus RKHC-28 AS QUORUM
SENSING INHIBITORS
Diana Martinez Matamoros1, Leonardo Castellanos1, Freddy Ramos1, Carmenza
Duque1, Catalina Arevalo-Ferro2
2
1
Department of Chemistry, Universidad Nacional de Colombia, 1111321, Bogota, Colombia.
Department of Biology, Faculty of Science, Universidad Nacional de Colombia, 1111321, Bogota,
Colombia.
Quorum sensing inhibitors (QSI) have shown a great potential to become into
therapeutic agents for treatment of some diseases caused by bacteria1, and as additives
in formulation of antifouling coats2.
Marine bacteria are a promissory source of QSI compounds, QS phenomenon is the
basis of interactions between bacteria and the eukaryotic host and other bacteria present
in host surface.3,4 In the present work, we evaluated 15 bacterial strains extracts
belonging to Firmicutes phylum, previously isolated from the octocoral
Pseudopterogorgia elisabethae (SW Caribbean sea, Colombia), as source of QSI
compounds. Each bacterium was cultured in four different liquid media, extracted with
organic solvent and tested as QSI using Cromobacterium violaceum ATCC 31532 as
biosensor. The strain Jeotgalicoccus halophilus RKHC-28 showed the best QS
inhibition activity. Additionally, chemical compounds produced by this bacterium have
not yet examined.
J. halophilus was cultured in Luria Bertani with marine salts (LBS) broth medium, and
extracted with DCM. The organic extract was separated by column chromatography
using Diol as stationary phase. Bioguided methodology allowed the isolation of five
compounds, which were identified by NMR, UV and MS. The isolated compounds
include phenolic derivatives: 4-(methylthio)phenol and p-hydroxybezaldehyde; indolic
derivatives: 3-indolaldehyde and (1-H-indol-3-yl)oxoacetamide; and an aliphatic amide
2-methylpropanoamide beside a non-ribosomal peptide partially characterized. A strong
QSI activity was observed for compounds (0.36, 0.41, 0.68, 1.06 and 1.14 mM,
respectively) using the biosensor C. violaceum and Dobretsov multi-well plate
methodology3. The known QSI compound kojic acid was used as positive control (1.4
mM).
Posters Session 2
References
1.
2.
3.
4.
Kalia, V.C. Quorum sensing inhibitors: An overview. Biotecnol. Adv. 2013, 31, 224.
Dobretsov S, Teplitski M, Paul V. Mini-review: quorum sensing in the marine environment and its
relationship to biofouling. Biofouling. 2009.25, 413-427.
Dobretsov, S.; Teplitski, M.; Bayer, M.; Gunasekera, S.; Proksch, P.; Paul, V. J. Inhibition of marine
biofouling by bacterial quorum sensing inhibitors. Biofouling 2011, 27, 893-905.
Goecke, F.; Labes, A.; Wiese, J., Imhoff JF. Chemical interactions between marine macroalgae and
bacteria. Mar. Ecol. Prog. Ser. 2010, 409, 267-300.
Acknowledgments
Financial
Support:
COLCIENCIAS
(Proyect:
110148925103,
contract:
BIOPROSPECCIÓN DEL CORAL BLANDO Pseudopterogorgia elisabethae. FASE IV
178
402-2009)
Posters Session 2
P 114
MICROALGAE BIOREFINERY. PRODUCTION BIOFUELS AND
PHARMACEUTICAL PRODUCTS
M. Martínez, E. Peña, N. Boulifi and J. Aracil
Group of Design, Optimisation and Scale-Up of Integrated Chemical and Biochemical Processes
(DOSIP), Chemical Engineering Department,. Complutense University, Madrid, Spain.
Microalgae are a heterogeneous group of organisms with a host of characteristics that
distinguish them, some of those being cell size, colour, inhabitation of aquatic
environment, as well as being unicellular and quite often, photoautotrophic.
The microalgae produce many valuable products, developing integrated microalgae
processing (MAP) for the sequential production of various products from the same
microalgae biomass can substantially reduce the cost of production, which in turn will
make it a profitable enterprise. For example, as the first step in an MAP concept,
harvested microalgae mass and culture water can be processed for recombinant protein
production. In the second step, the microalgae oil and microalgae meal can be
processed. From the algal oil, high-value omega-3 fatty acids, such as docosahexaenoic
acid and eicosapentaenoic acid, can be separately processed. The rest of the oil can be
used for biofuel production. Microalgae biomass can yield many coproducts from the
same biomass and this multiproduct paradigm makes it a perfect candidate for the
biorefinery concept. By producing various coproducts such as recombinant protein,
omega-3 fatty acids and biodiesel in a sequential biomass processing, an microalgae
biorefinery takes advantage of the various components in raw material and their
intermediates therefore maximizing the value derived from the biomass feedstock.
The DOSIP Group has been developed a know-how that involves the use of microalgae
for the production at laboratory scale of fatty acids, biodiesel and also value-added coproducts like: and carotenes and its derivatives, lutein, astaxanthin, canthaxanthin
(anti- Inflammatory effect in human) and also other pharmaceutical products with more
value-added than the aforementioned.
References
2.
Schenk PM, Hall SRT, Stephens E, Marx UC, Mussgnug JH, Posten C, et al. Second generation
biofuels: High-efficiency microalgae for biodiesel production. Bioenergy research 2008;1:20-43.
-Takaichi A. Carotenoids in Algae: Distributions, Biosyntheses and Functions. Marine Drugs
2011;9:1101-1118.
Posters Session 2
1.
179
P 115
Posters Session 2
ANTICANCER POTENTIAL OF FILAMENTOUS AND PICOPLAKTONIC
CULTURABLE MARINE CYANOBACTERIA: CYTOTOXICITY AGAINST
TUMOUR CELLS
Rosário Martins1,2,, Margarida Costa2, Pedro N. Leão2, João Costa-Rodrigues3,
Mónica Garcia3, Piedade Barros1, Helena Fernandes3, Vitor Vasconcelos2,4
1
CISA,Centro de Investigação em Saúde e Ambiente, Escola Superior de Tecnologia da Saúde do
Porto, Instituto Politécnico do Porto, Rua Valente Perfeito 322, 4400-330 Vila Nova de Gaia, Portugal.
2
CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Rua dos
Bragas 289, 4050-123 Porto, Portugal. 3Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr.
Manuel Pereira da Silva, 4200-393 Porto, Portugal. 4Faculdade de Ciências, Universidade do Porto,
Departamento de Biologia, Rua do Campo Alegre, Edifício FC4, 4169-007 Porto, Portugal.
From the marine cyanobacteria culture collection of the Laboratory of Ecotoxicology
Genomics and Evolution - CIIMAR, Porto, Portugal, twenty-eight strains of the
picoplanktonic genera Cyanobium, Synechocystis and Synechococcus, and the
filamentous genera Leptolyngbya, Pseudoanabaena and Romeria, were screened in
order to infer about their potential as producers of compounds cytotoxic to cancer cell
lines. Cytotoxicity of a crude extract and three fractions reflecting a preliminary
segregation of lipophilic metabolites was evaluated by MTT in a battery of human
tumour cell lines. Positive results were confirmed by the LDH assay. Eleven of the
studied strains showed to significantly inhibit the proliferation of the cancer cells.
Apoptosis/Necrosis was investigated by the dye exclusion method, using both Propidum
Iodide and Hoechst 33342 and by measuring Caspase -3 activity. From the Cyanobium
sp. strain LEGE 06113 it was already possible to isolate Hierridin B, previously isolated
from a Phormidium ectocarpi (1), which showed selective toxicity to HT-29 colon
adenocarcinoma cell line.
References
Papendorf O, König GM, Wright AD (1998) Hierridin B and 2,4-dimethoxy-6-heptadecylphenol, secondary metabolites from the cyanobacterium Phormidium ectocarpi with
antiplasmodial activity. Phytochemistry 49: 2383-2386.
Posters Session 2
1.
180
Posters Session 2
P 116
BIOACTIVE MICROORGANISMS ISOLATED FROM SOUTH AFRICAN
MARINE INVERTEBRATES
William Mavengere, Lucas Black, Gerda Du Plessis, Reyhana Hoosen, Timothy
Klein, Relebohile Matobole, Marla Tuffin
UWC, IMBM, New Life Science Building , University Of The Western Cape, 7535, Cape Town, South
Africa
Posters Session 2
The 1 535 539 km2 maritime jurisdiction referred to as the South African Exclusive
Economic Zone (SAEEZ) exhibits a significant level of biodiversity, though little is
known pertaining to the microbial component. Marine invertebrates are consistently
exposed to the open water and therefore, produce complex natural products to control
and defend against pathogenic microorganisms. Symbiont microorganisms, which can
make up to 35 % of the invertebrate biomass, have been shown to produce bioactive
natural products which help to protect the host. The objective of this study is to screen
for bioactive natural products produced by microbial symbionts isolated from endemic
South African marine invertebrates. Selected invertebrates are taxonomically distributed
into the phyla Annelida (worms), Chordata (sea squirts), Cnidaria (anemones),
Echinodermata (starfish and sea urchins), Mollusca (sea snails, limpets and mussels),
Platyhelminthe (flatworms), and Porifera (sponges). Representative members were
sampled from Kalk Bay (Western Cape, South Africa), and Algoa Bay (Eastern Cape,
South Africa). Preliminary isolate identification was based on Gram staining, colony
colour, size, shape and morphology.
Antimicrobial activity was determined based on the ability to inhibit the growth of
Mycobacterium smegmatis, Pseudomonas putida, Staphyloccocus aureus, Bacillus
cereus and an engineered multidrug resistant E. coli K12 strain. Bioactivity was
confirmed with solvent extractions and antibiosis. The bioactive isolates were identified
by 16S rRNA gene sequence analysis. This study demonstrates the quintessential role
that microorganisms play within biologically active molecule prospecting, as they
represent a sizeable component of all known ecosystems.
181
P 117
Posters Session 2
METAGENOMIC DISCOVERY OF BIOACTIVE COMPOUNDS FROM
ENDEMIC MARINE INVERTEBRATES OF SOUTH AFRICA
William Mavengere, Lucas Black.
UWC, IMBM, New Life Science Building , University Of The Western Cape, 7535, Cape Town,
Sudafrica
Posters Session 2
The vast South African coastline has high levels of marine endemism due to the unique
climatic and oceanographic environments. We are exploiting this fact to gain access to
previously uninvestigated marine invertebrates for the discovery of novel bioactive
compounds. A metagenomic approach allows us greater access to novel metabolic
pathways by removing the need to culture recalcitrant marine bacteria as the source of
many marine bioactive compounds. To our knowledge this is the first attempt to use a
metagenomic approach to identify bioactive compounds in South African marine
invertebrates (specifically from the Porifera and Urochordata). Libraries were prepared
using the pCCERI cosmid, for expression in multiple host organisms. Here we present
our initial results for the construction of large-insert metagenomic libraries from the
bacteria associated with endemic marine sponges and tunicates.
182
Posters Session 2
P 118
USE OF A GLOBAL METABOLIC APPROACH TO DISCRIMINATE
STRESSED FROM HEALTY CORALS
Fahoullia Mohamadi1, Isabelle Bonnard1, Cédric Bertrand1, Florence Nicolé2,
Christine Ferrier-Pagès3, Véronique Berteaux-Lecellier4, Patricia Wecker4, Bernard
Banaigs1
1
EA LCBE, Université de Perpignan, Laboratoire de Chimie des Biomolécules et de l’Environnement,
2
Université de Perpignan Via Domitia, 52 avenue Paul Alduy, 66860 Perpignan . EA 3061, Université
3
Jean Monnet, 35 Rue du 11 Novembre, 42023 Saint-Étienne. CSM, Monaco Laboratoires Direction
4
scientifique, Avenue Saint-Martin, MC 98000 Monaco-ville USR3278 CRIOBE, BP 1013 - 98729
Papetoai Moorea, Polynésie Française.
During the past three decades nearly 30% of the word’s coral reefs have been severely
degraded by bleaching1. Coral bleaching is a process whereby corals lose their algal
symbiont (zooxanthellae), or the symbiont’s photosynthetic pigments degrade2.
Understanding the mechanisms of bleaching is a real challenge as corals bleach under a
broad range of external stimuli such as increasing of sea temperature, light irradiance or
chemical pollution, that may occur sequentially or simultaneously3.
Metabolites, as the end products of metabolism, represent the functional responses of an
organism and reflect its physiological condition. With abiotic stresses, an alteration in
the molecular constituent is anticipated, characterization of which may form a basis for
bleaching diagnosis4.
We investigated a metabolomic approach for studying coral bleaching in order to
acquire a global view of bleaching mechanisms. We combined extraction of polar and
nonpolar metabolites with three fundamental and complementary analytical techniques,
GC/MS, LC/MS and NMR, to provide maximal coverage of the metabolome. We
focused on compounds that reflect coral physiological status for the improvement of the
chemical fingerprints acquisitions. After experimental method validation, we carried out
bleaching experiments in aquaria by increasing the temperature or light irradiance on
two scleractinian species. Multivariate statistical analysis were processed on the
chemical fingerprints with regard to their metabolite contents and levels5.
References
Posters Session 2
1. C.Wilkinson, in ‘Status of Coral Reefs of the World: 2004’, Chapter, 18 (2000), 473-491.
2. T. P. Hughes et al., Science 301 (2003), 929-933.
3. E Douglas, Marine pollution bulletin, 46 (2003), 385-92.
4. B van Ravenzwaay et al., Toxicology letters, 172 (2007), 21-28.
5. M.P.H. Verouden et al., Chemometrics and Intelligent Laboratory Systems, 98 (2009), 88-96.
183
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Posters Session 2
IDENTIFYING NATURAL PRODUCTS WITH AGONIST OR MODULATORY
ACTIVITY AGAINST HUMAN NUCLEAR RECEPTORS IN EXTRACTS
FROM CULTURED MARINE MICROALGAE
Angel Moldes-Anaya1,2, ThomasSæther2,4, Laila Norrheim-Larsen3, Hilde Irene
Nebb4,Terje Larsen1, and Steinar Martin Paulsen2
1
Cardiovascular Research Group, Institute of Medical Biology, University of Tromsø, Tromsø, Norway. 2
MabCent-SFI, University of Tromsø,Tromsø, Norway. 3 PronovaBiopharma*, Lysaker, Norway.
4
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo,Norway
Nuclear receptors (NR) are highly conserved transcription factors that regulate transcription in
response to small lipophilic molecules. These receptors regulate the expression of genes
involved in many critical processes such as embryonic development, metabolism and
inflammation. Dysfunctional signalling ofNRs is thought to be involved in diseases such as
cancer, diabetes, obesity and dyslipidemia. All these facts make NR attractive targets for
pharmacological intervention and development of therapeutics.
Several NR ligands with well-recognised biological effects are in clinical use, like the
hypolipidemic fibrates (e.g. Tricor®), acting as peroxisome proliferator-activated receptor alpha
(PPAR ) activators, and the anti-diabetic thiazolidine diones (e.g. Avandia®),targeting PPAR.
However, the negative side effects reported forthiazolidine diones point to the need of finding
new medicines for treating diseases like type-2 diabetes.
A bioassay-guided strategy for identification, purification and characterisation of PPAR ligands
from cultured microalgae is presented here. We are making use of biologically assay systems
incorporating unique protein targets to identify secondary metabolites possessing desirable
pharmacological profiles from extracts generated from microalgae cultures.
Posters Session 2
*PronovaBiopharma AS-now a part of BASF Group
184
Posters Session 2
P 120
IRVALEC, PIPECOLIDEPSIN A & STELLATOLIDE A: NEW MARINE
ANTITUMOR COMPOUNDS WITH NEW MECHANISMS OF ACTION
José M. Molina-Guijarro, Victoria Moneo, Juan F. Martínez-Leal, Carmen Cuevas,
Luis F. García-Fernández and Carlos M. Galmarini
Department of Cell Biology, Pharmamar S.A.U., Avda. de los Reyes 1, Madrid-28770, Spain.
Posters Session 2
Irvalec, Pipecolidepsin A and Stellatolide A are new marine-derived antitumor agents
with potent antitumor activity in vitro against a variety of human tumor cell lines.
Preliminary studies on the mechanism of action of these cyclic depsipeptides, showed
that all share common cellular effects on A549 (NSCLC) and HCT-116 (colon
adenocarcinoma) human tumor cells, causing rapid cell membrane permeabilization,
and necrotic cell death. In dose-response (DR) curves against a panel of 24 human
cancer cell lines, representative of 11 different tissues, the compounds showed GI50
values in the low micromolar range. Interestingly, all the compounds caused a notable
inhibition of tumor cell viability after 30 min of exposure, indicating that their cellular
effects were produced very rapidly upon treatment. Irvalec, the most extensively studied
compound, has been tested in Phase II clinical studies in patients with solid tumors. One
complete response was observed in one patient with large cell esophageal carcinoma
(24-hour q3wk schedule). Prolonged disease stabilization was also found in different
tumor types such as colorectal adenocarcinoma, pancreas adenocarcinoma, prostate
adenocarcinoma and STS among others. The efficacy of Pipecolidepsin A and
Stellatolide A is currently being evaluated in in vivo models. In summary, these results
indicate that the compounds Irvalec, Pipecolidepsin A and Stellatolide A may exert their
potent antitumor activity by inducing rapid and severe membrane damage in tumor
cells.
185
P 121
Posters Session 2
ANTIMICROBIAL PROPERTIES OF SEMISYNTHETIC OROIDINE AND
CLATHRODINE ANALOGUES
Sofia Montalvão1,2, Dorota Nawrot1, Nace Zidar3, iga Hodnik3, Ale ula3, Janez
Ila3, Lucija Peterlin Mai3, Danijel Kikelj3, Päivi Tammela1
1
2
Centre for Drug Research, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland;
Division of Pharmaceutical Biology, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki,
Finland; 3 University of Ljubljana, Faculty of Pharmacy, A kereva 7, 1000 Ljubljana, Slovenia
The ocean covers three-quarters of the Earth's surface and is home to an incredible
variety of flora and fauna, representing a wealth of resources for biotechnology research.
Marine organisms produce secondary metabolites that can be valuable for the
development of novel antimicrobial agents as such, but also by providing structural
scaffolds for the design and synthesis of novel antimicrobial compounds. As part of the
MAREX project1, two marine secondary metabolites, oroidine and clathrodine,
originally isolated from sponges of the genus Agelas, were used as scaffolds for the
design and synthesis of analogues. In total 39 analogues were initially screened for their
antimicrobial properties at 50 M concentration against C. albicans, E. coli, E. faecalis
and S. aureus by using a microdilution assay according to CLSI and EUCAST
guidelines. 14 compounds showed inhibition of growth by >80%, and these were
studied further by secondary assays, including MIC determination and cytotoxicity
against Huh-7 human hepatocellular carcinoma cell line. Seven analogues were found
active against S. aureus with MICs in the range of 12.5-50 M. Selectivity profiles
revealed significant differences between the analogues, which is important to consider
in the evaluation of their potential as antimicrobial leads.
Posters Session 2
1
This work was supported by the EU FP7 Project MAREX: Exploring Marine Resources for Bioactive
Compounds: From Discovery to Sustainable Production and Industrial Applications (Project No. FP7KBBE-2009-3-245137).
186
Posters Session 2
P 122
DEVELOPMENT OF INNOVATING BIOMEDICAL PRODUCTS FROM
MARINE RESOURCES VALORISATION THE MARMED PROJECT
J. Moreira-Silva, T.H. Silva, R.L. Reis
3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, AvePark, Zona Industrial da
Gandra S. Claúdio do Barco,4806-909 Caldas das Taipas - Guimarães, Portugal.
ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães; Portugal.
Posters Session 2
Marine resources can and should be managed in a sustainable manner. Every day subproducts and residues with high potential for valorisation are discarded. Particularly,
sub-products as fish bones can originate calcium phosphates and collagen; from
crustaceans exoskeleton and molluscs endoskeleton calcium phosphates and
chitin/chitosan can be obtained. From residues of algal blooms different polysaccharides
can be extracted. Once extracted and purified, these biopolymers and ceramics can find
application in different biomedical areas, such as biomaterials for human tissue
regeneration and/or for the release of bioactive compounds.
MARMED project aims the valorisation of marine sub-products from several
companies from the marine sector by isolation of marine origin biopolymers, ceramics
and bioactive compounds, which added-value and high-potential of applicability in
biomedical sector is demonstrated by the development of innovative applications. The
several research lines are carried on in close collaboration with industries (sub-products
generators, valorisation and biomedical) to increase the economic and market potential
of the proposed products and technologies, thus boosting their impact on society and
contributing to increase the awareness of blue biotechnological potential.
Some examples of valorisation strategies and biomedical applications being proposed
will be discussed, namely chitosan and collagen-based systems for human tissue
regeneration and drug delivery; marine bioceramics for bone tissue engineering;
bioactive compounds with antibacterial, anti-viral, antioxidant, pro-mineralisation
properties which can be isolated from algae and shellfish.
Finally, the contribution of MARMED to set bridges between companies generating
marine origin sub-products and the ones exploring biomedical products based in aquatic
origin materials will be highlighted.
187
P 123
Posters Session 2
CHEMICAL
C
HEMICAL S
STUDIES
TUDIES O
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AUSTRALIAN
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RALIAN NUDIBRANCHS
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Posters Session 2
References
R
eferences
Bobzin,
Bobzin, S.
S. C.;
C ; Faulkner,
C.
Faulkner, D.
D. J.
J. J.
J O
Org.
rg. Chem.
Chem. 1989,
1989 54,
54, 55727-5731.
727-5731.
-5731
Carmely, S.;
S.; Cojocaru,
Coojocaru, M.;
M.; Loya,
Loya, Y.;
Y.; Kashman,
Kashman, Y.
Y. J. O
rg. Ch
em. 1988, 53,
53, 44801-4807.
801-4807.
Carmely,
Org.
Chem.
Gulavita,
K.;; Gu
Gunasekera,
Nat.
Prod.
Gulavita, N. K.
nasekera, S.
S. P.;
P.; Pomponi,
Pomponi, S.
S. A. J. N
a t. P
rod. 1992, 55,
55, 5506-508.
06-508.
Fontana, A.;
A.; Trivellone,
Trivellone, E.;
E.; Mollo,
Mollo, E.;
E.; Cimino,
Cimino, G.;
G.; Avila,
Avila, C.;
C.; Martinez,
Martinez, E.;
E.; Ortea,
Ortea, J.
J. J.
J. Nat.
N a t.
Fontana,
Prod. 1994, 57,
57, 5510-513.
10-513.
Prod.
5 Tsubuki,
Tsubuki, M
.; Okita,
Okita, H.;
H.; Kaneko,
K aneko, K
.; Shigihara,
S h ig ih a ra , A
.; H
onda, T. Heterocycles
Heterocycles 2009, 77, 4433335)
M.;
K.;
A.;
Honda,
444.
11)
2
2)
3
3)
4
4)
188
Posters Session 2
P 124
NEW HYBRID PYRROLE-IMIDAZOLE ALKALOIDS FROM THE MARINE
SPONGE Agelas sceptrum STRUCTURE ELUCIDATION, SYNTHESIS, AND
BIOACTIVITY
1
2
2
1
Julie Munoz , Rodrigo Rodriguez , Phil S. Baran , Matthias Köck
1
Alfred-Wegener-Institut, Helmholtz-Zentrum Für Polar-Und Meeresforschung, Am Handelshafen 12,
27570, Bremerhaven, Germany. 2The Scripps Research Institute, Department of Chemistry, 10550
North Torrey Pines Road, La Jolla, Ca 92037, USA
Pyrrole-imidazole alkaloids (PIAs) have been to date exclusively isolated from marine
sponges. They have drawn attention of marine natural products chemists for almost 50
years due to their high diversity and interesting biological activities [1-3]. Although,
these compounds are architecturally complex and highly cyclized, the PIA structures are
all assumed to arise from the key intermediate oroidin through an unifying biosynthesis
[1,4]. Only a few congeners of the PIA family have yet been isolated as hybrid
compounds [PIA/non-PIA] such as nagelamide K [5] and taurodispacamide [6]. In all
cases the non-PIA moiety was always a taurine structural element. Herein we report for
the first time hybrid PIA derivatives from the marine sponge Agelas sceptrum
originated from an atypical merge with an oxoadenine moiety for 1 and a 3-amino-2amino-3-hydroxyphenyl moiety for 2. The structure elucidation including the relative
configuration of 1 and 2, the synthetic strategy of 1, and the biological relevance of both
structures are discussed.
References
2.
3.
4.
5.
6.
Köck, M.; Grube, A.; Seiple, I. B.; Baran, P. S. The pursuit of palau’amine. Angew.Chem. Int.
Ed., 2007, 46, 6586-6594.
Forte, B.; Malgesini, B.; Piutti, C.; Quartieri, F.; Scolaro, A.; Papeo, G. A submarine journey: the
pyrrole-imidazole alkaloids. Mar. Drugs, 2009, 7, 705-753.
Al-Mourabit, A.; Zancanella, M. A.; Tilvi, S.; Romo, D. Biosynthesis, asymmetric synthesis, and
pharmacology, including cellular targets, of the pyrrole-2-aminoimidazole marine alkaloids. Nat.
Prod. Rep., 2011, 28, 1229-1260.
Al Mourabit, A.; Potier, P. Sponge"s molecular diversity through the ambivalent reactivity of 2aminoimidazole: A universal chemical pathway to the oroidin-based pyrrole-imidazole alkaloids
and their palau"amine congeners. Eur. J. Org. Chem., 2001, 237-243.
Araki, A.; Kubota, T.; Tsuda, M.; Mikami, Y.; Fromont, J.; Kobayashi, J. Nagelamides K and L,
dimeric bromopyrrole alkaloids from sponge Agelas species. Org. Lett., 2008, 10, 2099-2102.
Fattorusso, E.; Taglialatela-Scafati, O. Two novel pyrrole-imidazole alkaloids from the
Mediterranean sponge Agelas oroides. Tetrahedron Lett., 2000, 41, 9917-9922.
Posters Session 2
1.
189
Posters Session 2
190
Posters Session 2
P 125
Posters Session 2
P 126
TOWARD PRACTICAL, EASY AND HIGH YIELD PRODUCTION OF
VIOLACEIN PRODUCED BY MARINE SPONGE-ASSOCIATED BACTERIA
Pseudoalteromonas luteoviolacea
Vassana Musa1,2, Chutiwan Dechsakulwatana3, Preecha Puwapraisirisan2
1
Program in Biotechnology, Faculty of Science, Chulalongkorn University, Phyathai Road, Patumwan,
Bangkok 10330, Thailand. 2Natural Product Research Unit, Department of Chemistry, Faculty of Science,
Chulalongkorn University, Phyathai Road, Patumwan, Bangkok 10330, Thailand. 3Institute of Marine
Science, Burapha University, Chonburi 20131, Thailand.
Marine sponge-associated bacteria are of considerable current interest as a new and
promising source of biologically active compounds. They produce a variety of
metabolites, some of which can be used for drug development. Violacein, a violet indole
alkaloid produced by several bacterial strains, has attracted much attention in recent
literature due to its promising bioactivities such as broad antibacterial, strong
bactericidal, antitumor, antiviral, antioxidant and antiprotozoan activities. Therefore,
effective violacein production has been developed to address urgent need of large scale
supply. However, the development has been limited due to end-product inhibition of
violacein. In this study, five different adsorbent resins, namely HP20, XAD4, XAD7,
XAD16 and XAD1180 were evaluated for efficiency to enhance violacein production
from marine bacteria, Pseudoalteromonas luteoviolacea which isolated from gulf of
Thailand. XAD1180 enhanced the highest yield, particularly when a 2% w.v-1
XAD1180 of the resin was added to medium after 16 h of cultivation. Partially purified
violacein (70%) could be easily isolated by washing the resin with methanol. This
method could produce 2-fold increment in violacein production when compared with
conventional fermentation and maximum yield of violacein was up to 3.285 g.L-1. The
use of adsorbent resin in violacein production not only enhanced product yield but also
facilitated isolation of violacein from aqueous media. Our approach also serves as an
environmentally friendly method for cultivation of bacteria producing bioactive
metabolite.
Posters Session 2
Keywords: Marine sponge-associated bacteria, Violacein, Pseudoalteromonas luteoviolacea, Adsorbent
resin, Indole alkaloid.
References
1.
Xing, X.H., Lu, Y., Wang, L., Xue, Y., Zhang, C., Lou, K., Zhang, Z., Li, Y., Zhang, G., Bi, J.
and Su, Z. 2008. Production of violet pigment by a newly isolated psychrotrophic bacterium
from a glacier in Xinjiang, China. Biochemical Engineering Journal. 43: 135-141.
191
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Posters Session 2
BIOACTIVITY OF METABOLITES FROM ANTARCTIC BENTHIC
INVERTEBRATES: DOES ENERGETIC CONTENT INTERACT WITH
FEEDING REPELLENTS?
Laura Núñez-Pons1, Marianna Carbone2, Margherita Gavagnin2 and Conxita Avila1
1
Departament de Biologia Animal (Invertebrats), Facultat de Biologia, Universitat de Barcelona, Av.
Diagonal 643, 08028 Barcelona, Catalunya, España. 2Istituto di Chimica Biomolecolare, CNR, Via
Campi Flegrei 34, I 80078-Pozzuoli, Napoli, Italia.
[email protected]
Posters Session 2
Antarctic benthic communities are rich sources of bioactive natural products. The
production and/or presence of these compounds presumably evolved and was
maintained in sessile, sluggish invertebrates as means of protection. Shelf benthic
organisms make use of such metabolites as chemical defenses, to mediate ecological
interactions and combat intense episodes of predation. Regarding chemicals with
feeding repellent properties, these have been well studied, even if seldom have the
involved molecules been chemically identified. It is suggested, yet scarcely proved, that
protective activities provided by some metabolites interfere with the nutritional quality
of prey harboring the compounds. This means that antifeedants would become less
effective when combined with energetically rich food items. Moreover, chemicals of
different nature provide bioactivities of distinct potency. We evaluated the effectivity of
five types of repellents obtained from Antarctic invertebrates, in combination with diets
of diverse energetic value. The metabolites tested came from several species of soft
corals, ascidians and hexactinellid sponges, and included wax esters, alkaloids,
meroterpenoids, steroids, and a newly reported organic acid. This last compound
represents the first secondary metabolite ever obtained from glass sponges. Feeding
preference assays were performed preparing alginate caviar-pearls containing different
food source concentrations, and treated with various concentrations of each product.
These pearls were offered to the circumpolar omnivore amphipod Cherimedon
femoratus, to determine feeding repellence. We observed significant variability in the
effect of the diverse types of repellents, and in relation with pearls’ nutritional content.
Our results reflect that energetic value affects the activity of certain chemical defenses.
192
Posters Session 2
P 128
COMPOSITION AND QUANTITATION OF MICROALGAL LIPIDS BY
ERETIC 1H NMR METHOD
Genoveffa Nuzzo, Carmen Gallo, Adele Cutignano, Giuliana D’ippolito, Angelo
Fontana
Cnr-Istituto di Chimica Biomolecolare, Via Campi Flegrei, 34, 80078, Pozzuoli, Naples, Italy.
The importance of microalgae as a source of fatty acids (FAs) and fatty acid derivatives
(FADs) has been long claimed.1 The attention for these compounds has been further
increasing as consequence of the consideration that microalgae can be suitable source of
functional health products (chemicals, drugs, vitamins, etc.) or third generation biofuels.
Composition of algal lipids depends greatly on genetic and phenotypic factors.2
Traditional approaches for the quantification of lipid from microalgae rely on labor and
intensive methods, such as solvent extraction and gravimetric determination.3 Nile Red,
a lipid soluble fluorescent dye, is frequently used to estimate neutral lipids.4 However,
this assays is not of universal application. Spectroscopic methods, including Fourier
transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1HNMR) have been also reported to monitor the products of transesterification reaction.5,6
We discuss a simple procedure based on 1H NMR spectroscopy for identification and
quantification of different species of lipids in rough microalgal extracts. Quantitative
assessment was established by the ERETIC method in agreement with reference 7.
The method offers a rapid assessment of content and composition of major lipid classes,
including triglycerides (TAG), phospholipids (PL), glycolipids (GL) and free fatty acid
(FFA), that permits the routinely analysis of large number of samples.
We analyze the lipid extracts of the microalgae Thalassiosira weissflogii (TW),
Nannochloropsis salina (NS) and Cyclotella cryptica (CYC), which belong to different
taxonomic classes and are featured by different lipid compositions.8
Full analysis of microalgal samples takes only a few minutes and could be fully
automatized.
References
3.
4.
5.
6.
7.
8.
Radwan SS. Applied Microbiology and Biotechnology; 1991; 35: 421-430.
Stuart AS, Matthew PD, John SD, Irmtraud H, Christopher J, Lea-Smith DJ, Alison GS. Current
Opinion in Biotechnology; 2010; 21: 277-286.
Bligh EG, Dyer WJ. Canadian Journal of Biochemistry and Physiology; 1959; 37: 911-917.
Chen W, Zhang C, Song L, Sommerfeld M, Hu Q. Journal of Microbiology Method; 2009; 77:
41-47.
Zagonel GF, Zamora PP, Ramos LP. Talanta 2004; 63: 1021-5.
Neto PRC, Caro MSB, Mazzuco LM, Nascimento MG. Journal of the American Oil Chemists"
Society 2004; 81: 111.
Akoka S, Barantin L, Trierweiler M. Analytical chemistry. 1999; 71: 2554-2557.
Pahl SD, Lewis DM, Chen F, King KD. Journal of Applied Phycology, 2010; 22:165-171;
Prartono T, Kawaroe M, Katili V. International Journal of Environment and Bioenergy; 2013;
6(1): 28-43; Mohammady NG. Journal of biosciences; 2011; 66(7-8): 328-32.
Posters Session 2
1.
2.
193
P 129
Posters Session 2
HUGE RING SIZE MACROLIDE FROM MARINE DINOFLAGELLATE OF
THE GENUS Symbiodinium
Ken-Ichi Onodera
Kochi University, Kohasu, Oko, Nankoku, 783-8505, Kochi, Japan.
Marine dinoflagellates, unicellular phytoplankton, produce numerous bioactive and
complex secondary metabolites. The genus Symbiodinium, belonging to the
zooxanthellae, is the most representative dinoflagellate, living symbiotically in a wide
range of marine invertebrates. In the course of studies on the search for the bioactive
secondary metabolites, we succeeded in determining the structure of zooxanthellamide
Cs which contain the components with the largest macrolactone ring size (66membered) and have high molecular weight (ca. 2700)1.
A further search for the Symbiodinium metabolites resulted in the isolation of a new
polyhydroxy compound which exhibited a pseudomolecular ion at m/z 2860 in the
negative MALDI-TOF-MS. The metabolite was isolated from zooxanthellae of
flatworm together with zooxanthellatoxins2. It has a macrolactone ring with a sulfate
group and a spirocyclic moiety was identified by the structural analysis with 1D and 2D
NMR. The metabolite was mainly composed of two parts, a large macrolactone part and
a long chain part, revealed by detailed NMR analysis. Further studies on the structure
and biological activity of the metabolite are in progress.
References
1.
Posters Session 2
2.
Onodera K., Nakamura H., Oba Y., Ohizumi Y., Ojika M., J. Am. Chem. Soc., 2005, 127,
10406-10411.
Nakamura H., Asari T., Murai A., Kan Y., Kondo T., Yoshida K., Ohizumi Y., J. Am.
Chem. Soc., 1995, 117, 550-551.
194
Posters Session 2
P 130
WHAT ABOUT THE ABILITY OF THE MEDITERRANEAN BROWN
SEAWEED Taonia atomaria TO CONTROL FOULERS BUT ALSO TO SELECT
SURFACE-ASSOCIATED BACTERIA?
Ahlem Othmani, Jean-François Briand, Maëlle Molmeret, Annick Ortalo-Magné,
Yves Blache and Gérald Culioli
Laboratoire MAPIEM (EA 4323), «Biofouling & Substances naturelles marines», Université du Sud
Toulon-Var, ISITV, Avenue Georges Pompidou, BP 56, 83160 La Valette-du-Var Cedex, France.
Marine biodiversity is an inexhaustible source of bioactive compounds in various areas
but much to be done in the interpretation of their ecological roles [1-3]. The aim of this
work was to investigate the anti-adhesion properties of natural substances isolated from
the brown alga Taonia atomaria, collected on the French Mediterranean coast (Var,
France), and, as part of this work; to comprehend the strategies of biofilm regulation at
its surface.Molecules from the organic crude extracts were characterized as simple
lipids and sesquiterpens, some of them being new from the interpretation of their
spectral data. Surface-associated metabolites were assessed after the development of a
specific extraction protocol based on the choice of a suitable organic solvent and the
appropriate time of exposure keeping the integrity of the algal surface cells. The
majority of isolated compounds were tested in laboratory anti-adhesion assays against
some bacterial strains isolated from the surface of T. atomaria, and some reference
strains coming from artificial substrata. The obtained results showed that reference
commercial biocides and compounds from the whole-extract of T. atomaria exhibited a
similar effect on all bacterial strains. Interestingly, the main surface metabolite showed
no effect against surface-associated bacteria while it seemed to inhibit significantly the
settlement of reference strains.
Further experimentations are in progress to test the effectiveness of these surfaceassociated metabolites against a large panel of bio-foulers and to explore if chemical
cues from associated bacterial communities could be implicated in the biofilm control
by T. atomaria.
References
Andras et al (2012). J. Chem. Ecol. 38 (10): 1203-1214.
De Nys et al (1998). Mar. Ecol. Prog. Ser. 162: 79-87.
Suddati et al (2008). J. Phycol. 44 (3): 584-591.
Posters Session 2
1.
2.
3.
195
P 131
Posters Session 2
AN
A
N EFFICIENT
EF
FFICIENT A
AND
ND VERSATILE
VERSATILE CHEMICAL
CHEMICAL SYNTHESIS
SYNTHESIS OF
OF BI
BIOACTIVE
OACTIVE
GLY
YCOGLYCEROLIPIDS
GLYCOGLYCEROLIPIDS
Dario Pagano,
Pagano, Em
Emiliano
E
iilliano M
Manzo
an
a zo an
andd Angelo
Ange
g lloo Fon
Fontana
taana
Dario
Institute
In
stitute ooff Bi
Biomolecular
omolecular Ch
Chemistry
emistry ((National
National Co
Council
uncil ooff Re
Research),
search), via
via campi
campi flegrei
flegrei 3-80078,
3-80078, Pozzuoli,
Pozzuoli,
Na
ples, Italy.
Italy.
Naples,
E-m
mail: [email protected]
[email protected]
E-mail:
Posters Session 2
Glycogllycerolipids have
Glycoglycerolipids
haavve important
important structural
structuural functions
func
u tions and
and play
an
playy a role
role as
as signalling
signalling
m
oleculles iinn ccellular
ellularr m
echaannisms. G
alactosyl-mono- and
and di-acylglycerols
d acylglycerols are
diarre about
abbout 70molecules
mechanisms.
Galactosyl-mono80% of membrane
membraanne lipids
lipids in
in photosynthetic
photos
o ynthetic cells
cells representing
representing
n the
the most
most abundant
abunda
b
nt class
class of
llipids
ipids in
in the
the biosphere.
biosphere. In recent
recent
n years,
years, natural
naatural and
annd synthetic
synnthetic derivatives
derivattives of monomonoo
(M
GDG) and
annd di-galactosyl
di-galactosyl (DGDG)
(DGDG) diacylglycerols
diacylglycerols have
haavvee attracted
atttracted the
the interest
interest off the
thhe
(MGDG)
bi
o-medi
d cal ccommunity
ommunity due ttoo ttheir
heir bi
ological prope
rties aass antiviral,
anntiviral, antitumor
anntituumor and
annd
bio-medical
biological
properties
aanti-inflammatory
nnti-infflammatory activity.
activityy.1 Furthermore,
Furt
u hermore, studies
studies about
abouut immunological
immunological response
respoonse
activated
activaated by MGDG/DGDG
MGDG/DGDG showed
showed a specific
specific dependence
depe
p ndence on the
the structural
structural
characteristics
chaara
r cteristics of these
these substances.
substanncces. It has
has been
been recently
recently shown
shown that
thaat recognition
recognitionn of
MGDG and
annd DGDG
DGDG by natural
naatural killer
kiiller T cells
cells iiss sstrictly
trrictly de
peendent on tthe
he ccomposition
ompositionn of
MGDG
dependent
fatty
fat
atty acids.
acids.2 T
The
he hi
high
gh specificity
specificity of this
this interaction
interaction requires
requirees an
an accurate
accuratte purification
purificattionn of
antigenic
preparation
anntiggeniic llipids
ippids and
annd in
in this
this context
context a chemical
chemical ppre
ppaarraationn iiss aann eessential
ssential step
step for
for
o the
thhe
evaluaation of their
their immune-modulating
immune-moddulating activity.
activity. Here
Here we
we discuss
discuss an
an improved
improved and
annd
evaluation
versatile sstrategy
trraategy ffor
or
o tthe
he ssynthesis
yntthhesis of -galactosyl-galactosyl- and
and
n -gl
lucosyl aanalogs
na
n logs of m
ono- and
annd
versatile
-glucosyl
monodiacylgllycerols containing
containing both
botth saturated
saturatted and
annd unsaturated
unsatturatted fatty
fat
atty acids.
acids.3 Synthesis
Synthesis iiss
diacylglycerols
aachieved
chieved by ttrichloro-acetimidate
richloro-acetimidaate m
ethodology and
annd use
use of
of peracetate
peracetate sugar
sugar substrates.
substraates.
methodology
T
he ssynthetic
ynnthetic approach
appproach is
is designed
designned to
to obtain
obtain enantiomerically
enaanntiomerically pure regio
regio and
and stereostere
r oThe
iisomers
somers including
including derivatives
derivaatives containing
conntaining poly-unsaturated
poly-unsatturated fatty
fatty acids.
acids.
References:
Re
feren ces:
1. (a
((a)Máñez,
)Máñez, S.;
S.; Recio,
Recio, M.
M. C.;
C.; Gil,
Gil, I.;
I.; Gómez,
Gómez, C.;
C .; G
iner, R.
R. M.;
M.; Waterman,
Waterman, P.
P. G.;
G.; Ríos,
Ríos, J.
J. L.
L. J. N
a t.
Giner,
Nat.
Pr
od. 1999
2, 6601-604;
01-604; ((b)
b) B
erge, JJ.. P
.; D
ebiton, E
.; D
umay, J.;
J .; D
urand, P
.; B
arthomeuff, C
Prod.
1999,, 662,
Berge,
P.;
Debiton,
E.;
Dumay,
Durand,
P.;
Barthomeuf,
C.. JJ..
Ag
ric. Fo
od Chem.
Chem. 2002
0, 6227-6232;
6227-6232; (c)
(c) Larsen,
Larsen, E.;
E.; Kharazmi,
Kharazmi, A.;
A.; Christensen,
Christensen, L.
L. P.;
P.;
Agric.
Food
2002,, 550,
Ch
ristensen, S.
S. B. J. N
a t. P
rod. 2003
6, 9994-995;
94-995; (d)
(d) Seki,
Sekii, Y.;
Y.; Hayashi,
Hayashi, K.;
K.; Matsumoto,
Matsumoto, A.;
A .;
Christensen,
Nat.
Prod.
2003,, 666,
Se
ki, N.;
N.; Tsukada,
Tsukada, J.;
J.; Ransom,
Ransom, J.;
J.; Naka,
Naka, T.;
T.; Kishimoto,
Kishimoto, T.;
T.; Yoshimura,
Yoshimura, A.;
A.; Kubo,
Kubo, M.
M. Proc.
P oc.
Pr
Seki,
Na
tl. A
cad. SSci.
ci. 2002
9, 113003-13008.
3003-13008.
Natl.
Acad.
2002,, 999,
2 Ki
K
njo, Y.;
Y.; Illarionov,
Illarionov, P.;
P.; Vela,
Vela, J.
J. L.;
L.; Pei,
Pei, B.;
B.; Girardi,
Girardi, E.;
E.; Li,
Li, X.;
X.; Li,
Li, Y.;
Y.; Imamura,
Imamura, M.;
M.; Kaneko,
Kaneko,
Kinjo,
Y
Y.
awara, A.;
A.; Miyazaki,
Miyazaki, Y.;
Y ; Gomez-Velasco,
Y.
Gomez-Velasco, A.
ogers, P.;
P.; Da
hesh, S.;
S.; Uchiyama,
Uchiyama, S.;
S .;
Y.;; Ok
Okawara,
A.;; R
Rogers,
Dahesh,
K
Kh
urana, A.
wahara, K.
esilkaya, H.
drew, P
.; W
ong, C
a w a k a m i, K
.; N
iz e t,
Khurana,
A.;; Ka
Kawahara,
K.;; Ye
Yesilkaya,
H.;; An
Andrew,
P.. W
W.;
Wong,
C.. H.
H.;; K
Kawakami,
K.;
Nizet,
V
V.
Besra, G. S.;
S.; Tsuji,
Tsuji, M.;
M .; Z
ajonc, D. M.;
M.; Kr
onenberg, M.
M. Na
t. Im
munol. 2011
2(10), 996666V.;; Besra,
Zajonc,
Kronenberg,
Nat.
Immunol.
2011,, 112(10),
9974
974.
3. Ma
a n z o ,E .; C
iavatta, M.
L .; P
agano, D.;
D .; F
ontana, A.
A. Te
trahedron Letters,
Letters, 2012, 53
79-881.
Manzo,E.;
Ciavatta,
M.L.;
Pagano,
Fontana,
Tetrahedron
53,, 8879-881.
196
Posters Session 2
P 132
NEW -CARBOLINE ALKALOIDS FROM THE TROPICAL SPONGE Hyrtios
sp.
Seungil Park, Hyi-Seung Lee
KIOST, Marine Natural Products Laboratory, 787 Haeanro, 426-744, Ansan, South Korea.
Much attention has been focused on -carboline alkaloids owing to their potential utility
and significant biological activity, such as antiviral, antimicrobial, antitumor and
insecticidal activity. Alkaloids containing the -carboline skeleton have been isolated
from marine invertebrates, which include hydroids, bryozoans, tunicates, and various
sponges. The -carboline alkaloids obtained from marine organisms frequently possess
novel frameworks while in other cases terrestrially related compounds clearly exist.
Their structure elucidation, chemical modification, and synthesis have received a great
deal of interdisciplinary attention from areas of research other than chemistry and
include pharmacology and medicine. Marine sponges of the genus Hyrtios have proven
to be a rich source of structurally diverse metabolites including alkaloids, mainly
sesterterpenes, sesquiterpene quinones, macrolides, tryptamine-derived alkaloids and carboline alkaloids. Many of them possess important biological activities. In the course
of our study on the chemical investigation of marine organisms, we found -carboline
alkaloids from the tropical sponge Hyrtios sp. collected in Chuuk State, Federated States
of Micronesia. Bioassay-guided separation of the crude extracts using various
chromatographic techniques yielded two new -carboline alkaloids, 6-hydroxy-9Hpyrido[3,4-b]indole-1-carboxylic acid (1) and (5-hydroxy-1H-indol-3-yl)(6-hydroxy4,9-dihydro-3H-pyrido [3,4-b]indol-1-yl)methanone (2), together with fifteen known 5hydroxyindol alkaloids from the extracts of Hyrtios sp. Their structures were elucidated
on the basis of mass spectrometry and 2D NMR spectroscopic data. The isolated
compounds were evaluated for their cytotoxic activities and anti-oxidant activity. The
additional biological activities will be described.
References
3.
Pedpradab, S.; Edrada, R.; Wray, V.; Proksch, P. J. Nat. Prod. 2004, 67, 2113-2116.
Lee, H. S.; Yoon, K. M.; Han, Y. R.; Lee, K. J.; Chung, S. C.; Kim, T. I.; Lee, S. H.; Shin, J.;
Oh, K. B. Bioorg. Med. Chem. Lett. 2009, 19, 1051-1053.
Inman, W. D.; Bray, W. M.; Gassner, N. C.; Lokey, R. S.; Tenney, K.; Shen, Y. Y.; TenDyke,
K.; Suh, T.; Crews, P. J. Nat. Prod. 2010, 73, 255-257.
Posters Session 2
1.
2.
197
P 133
Posters Session 2
SEARCHING NATURAL BIOACTIVE PRODUCTS FROM LICHENASSOCIATED BACTERIA
Delphine Parrot1, Laurent Intertaglia2, Clémence Rohee3, Sandrine David Le-Gal4,
Martin Grube5, Marcelino T Suzuki2, Sophie Tomasi1
1
UMR CNRS 6226, Universite Rennes 1, 2 Avenue Du Professeur Leon Bernard, 35000, Rennes, France.
2
UMR CNRS 7621 Université Paris 6, Banyuls Sur Mer, 66651, France. 3Pierre Fabre/UPMC/CNRS,
Banyuls Sur Mer, 66651, France. 4UPRES EA 1254 Université Rennes 1, Rennes, 35043, France. 5Institut
Für Pflanzenwissenschaften Université Karl-Franzens, Graz, 8010, Autria.
Posters Session 2
Efficiency of currently used antibiotics is worldwide decreasing at a worrying rate,
while we are faced with new and emerging pathogens. The majority of active natural
products are isolated of the Ascomycetes or of the Actinobacteria. Among the 10000
known antibiotics, more than half are produced by bacteria of one single genus,
Streptomyces. It is therefore most interesting to search for novel active molecules in yet
under explored niches, such as mutualistic microbial symbioses. Lichens are complex
organisms harboring bacterial communities on the surface and, more rarely, inside their
thalli. Three bacterial phyla are prevalent in this association: Proteobacteria,
Actinobacteria and Firmicutes. We focus on the cultivable bacterial communities
present on three lichens from Brittany coast (France) (Roccella fuciformis, Lichina
confinis, L. pygmaea) and one inland lichen from Austria (Collema auriforme) to find
new secondary metabolites of interest. These communities are dependent on several
extrinsic (environmental) and/or intrinsic parameters including the chemical
composition of their substrate (lichens).
The aims of this study were (1) to show the abundance and the diversity of the bacterial
communities associated to these lichens and (2) to elucidate the secondary metabolites
patterns of the lichens and some of their cultivable associated bacteria. 131 different
bacterial OTUs (operational taxonomic units) were isolated and identified by 16S rRNA
gene analysis from these lichens. More than 30% of all strains express potential
bioactive compounds and 10% represent probably new species. We study two of the
strains in greater detailed study as they produce potentially interesting and new active
secondary metabolites.
198
Posters Session 2
P 134
SINTHESYS OF 5 ,8 -EPIDIOXICOLEST-6-EN-3-OL DERIVATIES WITH
DIFERENTS AROMATIC ACIDS AND THEIR ANTI PLASMODIAL ACTIVITIES
Manuel Pastrana1, Alejandro Martínez1 & Silvia Blair2
1
Grupo Productos Naturales Marinos, 2Grupo Malaria. Universidad de Antioquia, Medellín-Colombia.
Epidioxysterols, part of the oxysteroids that have endoperoxide groups in their structure,
are compounds with interesting pharmacological properties[1]. Initially, they were found in
marine organism like sponges and tunicates and they have been of great interest in the
study of natural products mainly for their isolation, origin and properties. These compounds
have shown a great diversity of pharmacological properties such as antiproliferative,
antitumor, antiparasitarys, anti incrustant and bactericidal[2]. It has been proposed that the
pharmacological mechanism of them is related with the release of the singlet oxygen by the
retro Diels-Alder addition from which a free radical is produced. This radical is very
reactive and it can affect many of the cellular components. Another hypothesis is that
oxysterols inhibit the synthesis of cholesterol, a component of the plasmatic membrane, in
the process of mitosis[3]. Compounds with the endoperoxide group have been effective in
the treatment of some parasites like P.falciparum. One of them is artemisinin[4], it is used in
the therapy of the infection of malaria. In this job we have present the synthesis of 5
derivatives of 5 ,8 -epidioxycholest-6-en-3-ol with aromatic acids, see figure 1, forming
ester bonds with the Steglich methodologies. Also, the results of their in vitro anti
plasmodial activities are shown. This activity was evaluated by the measurement of the
metabolism of [3H]-Hipoxantine as a source of purine compounds in this parasite.
Posters Session 2
Figure 1, 5 ,8 -epidioxicolest-6-en-3-ol derivatives with different aromatics acids
References
1. Bensemhoun, J.; Bombarda, I.; Aknin, M.; Faure, R.; Gaydou, E. M., 5 ,8 -Epidioxysterols from the
tunicate Didemnum salary. Biochemical Systematics and Ecology 2008, 36, 942-944.
2. Ioannou, E.; Abdel-Razik, A. F.; Zervou, M.; Christofidis, D.; Alexi, X.; Vagias, C.; Alexis, M. N.;
Roussis, V., 5 ,8 -Epidioxysterols from the gorgonian Eunicella cavolini and the ascidian
Trididemnum inarmatum: Isolation and evaluation of their antiproliferative activity. Steroids 2009,
74, 73-80.
3. C. Fernández, M.d.V.T. Lobo, D. Gómez-Coronado, M.A. Lasunción, Cholesterol is essential for
mitosis progression and its deficiency induces polyploid cell formation, Experimental Cell Research,
300 (2004) 109-120.
4. Kepler, J. A.; Philip, A.; Lee, Y. W.; Musallam, H. A.; Carroll, F. I., Endoperoxides as potential
antimalarial agents. Journal of Medicinal Chemistry 1987, 30, 1505-1509.
199
P 135
Posters Session 2
HIGH ANTITUMOR ACTIVITIES OF ISOLATED FRACTIONS FROM
SEAWEED Bifurcaria bifurcata COLLECTED ON THE PORTUGUESE COAST
Celso Alves, Raquel Pandeirada, Lurdes Fernandes, André Horta, Daniel Rodrogues,
Joana Silva, Susete Pinteus and Rui Pedrosa
GIRM – Marine Resources Research Group, Polytechnic Institute of Leiria, Peniche, Portugal.
Posters Session 2
Natural product compounds from various marine sources have often been found to be
promising pharmaceutical agents. In fact, the marine environment is an exceptional
reservoir of bioactive natural products, many of which exhibit structural/chemical
features not found in terrestrial natural products. Many of these compounds have
showed interesting antitumor activities.
The aim of this study was to evaluate the antitumor activity of isolated fractions
obtained from seaweed Bifurcariabifurcate on a human hepatocellular liver cell line
model (HepG-2 cells).
Nine fractions of Bifurcariabifurcata dichloromethane extracts were produced by
Vacuum Liquid Chromatography (VLC) using cyclohexane with increasing amounts of
10% of ethyl acetate. All of the VLC fractions were tested in HepG-2 cells through
cytotoxicity and anti-proliferative MTT assays. Cisplatin was used as positive control.
The highest cytotoxicity was exhibited by F8 and F9 fractions that reduced the HepG-2
cells viability (24 hours incubation) with an IC50 of 119.0 (88.6 – 159.9) and 57.81 g/ml
(30.5 – 109.8), respectively. The IC50 of crude extract and cisplatin were 123.9 (96.7 –
158.6) and 136.5 g/ml (116.5 – 159.9), respectively. In cell proliferation tests the
smallest IC50 was linked to the F7 and F8 fraction with 17.1 (11.3 – 25.9) and
18.3 g/ml (14.3 – 23.5). The IC50 of crude extract and cisplatin were 95.3 and 22.6
g/ml, respectively.
In conclusion, Bifurcariabifurcata seaweed can be a promising source of new molecules
with therapeutically applications in cancer pathology.
200
Posters Session 2
P 136
ANTIOXIDANT AND ATIMICROBIAL PROTENTIAL OF THE Bifurcaria
bifurcata EPIPHYTIC BACTERIA
Susete Pinteus1, Sara Fernandez2, André Horta1, Daniel Rodrogues1, Celso Alves1and
Rui Pedrosa1
1
2
Escuela técnica superior de ingeniería agraria (ETSEA), Universityof Lleida, Spain
Posters Session 2
Epiphytic bacteria living on the macro-algae surface can be a great source for the search
of new antioxidant and antimicrobial metabolites.
The aim of this study was the isolation of epiphytic bacteria of Bifurcaria bifurcata and
evaluation of the antioxidant and antimicrobial activity in order to understand if the
Bifurcaria bifurcata associated bacteria can be or not be linked to the high antioxidant
and antimicrobial activity found previously in this alga.
The antioxidant activity was evaluated by quantification of the Total Polyphenol
Contents, by measure the DPPH free radical scavenging activity and by the ORAC
assay using methanol:dichloromethane (1:1) extracts obtained from each of the bacteria
freeze dry biomass. The same extracts were also tested against S.aureus, B.subtilis, E.
coli 10536 and S. cerevisiae.
For the twenty different Bifurcaria bifurcate epiphytic bacteria extracts tested, only two
bacteria extracts (1mg/ml) reduced DPPH free radical more than 60%. All the bacteria
extracts had shown polyphenol contents less than 10 mg of acid gallic equivalents/g of
extract. By contrast, five bacteria showed more than 400 mol trolox equivalent/g of
extracts. Five and fourteen bacteria extracts (1mg/ml) completely blunted the S. aureus
and B. subtilis growth, respectively. No extracts showed high inhibition against E. coli
and S. cerevisiae.
In conclusion, Bifurcaria bifurcata bacteria extracts can be used as a source of
identification and purification of marine natural compounds with high antioxidant and
antibacterial activity.
201
P 137
Posters Session 2
ANTITUMOR AND ANTIMICROBIAL PROTENTIAL OF THE Asparagopsis
armata EPIPHYTIC BACTERIA
André Horta, Susete Pinteus, Celso Alves and Rui Pedrosa
Posters Session 2
Epiphytic bacteria living on the macro-algae surface can be a great source for new
molecules with antitumor and antimicrobial potential.
The aim of this study was the isolation of epiphytic bacteria of Asparagopsis armata
and the evaluation of the antitumor and antimicrobial activity of the isolated strains.
The antimicrobial activity was evaluated with the methanol:dichloromethane (1:1)
extracts obtained from each of the bacteria freeze dry biomass. The microbial targets
were S.aureus, B.subtilis, E. coli 10536, E. coli 1103, P. aureginosa, Salmonella sp., C.
albicansand S. cerevisiae. The antitumor potential was evaluated by the cell viability
and the cell proliferation analysis using the MTT assay. The cell lines used were the
HepG-2, Caco-2 and MCF-7 cells.
For all the three cell lines tested, none of the thirty different Asparagopsis armata
epiphytic bacteria extracts (1mg/ml) reduced more than 30% of the cell viability or cell
proliferation. On the other hand two extracts (1mg/ml) of different strains (ASP34 and
ASP124) inhibited more than 80% of the B. subtilis growth. The strains ASP2, ASP7
and ASP11 extracts also reduced over 80% of the S. aureus growth.
In conclusion, the Asparagopsis armata bacteria extracts can be used as a source of
identification and purification of marine natural compounds with high antibacterial
activity against S. aureus and B. subtilis.
202
Posters Session 2
P 138
EXERTING
EX
ERTING CIS-CONTROL
CIS-CONTROL OVER
OVER
R THE
THE PROLYL
PROLYL PEPTIDE
PEPTIDE BONDS:
BONDS: REREE
EVALUATION OF
OF P
HAKELLISTATINS BI
B
OACTIVITY
EVALUATION
PHAKELLISTATINS
BIOACTIVITY
M
aarta Pelay
Pelaay G
imeno1, Al
Alessandra
lessandr
d a Meli
Meli1, An
Andrés
drés Francesch
Francesch2, Car
Carmen
men Cu
Cuevas
evas2, Judit
Ju
udit
Marta
Gimeno
1
1
Tulla-Puche
Tulla-P
Puche , Fe
Fernando
rnando Albericio
Allbbericio
1
Institute
In
stitute ffor
or R
Research
esearch in
in Biomedicine,
Biomedicine, IRB
IRB Barcelona,
Barcelona, Baldiri
Baldiri Reixac,
Reixac, 110,
0, 008028,
8028, Barcelona,
Barcelona, Spain.
Spainn.
2
PharmaMar,
Ph
armaMar, S. A.,
A., Avenida
Avenida de
de los
los Reyes,
Reyes, 11,, 228770,
8770, Colmenar
Colmenar Viejo,
Viejo, Madrid,
Madrid, Spain.
Spain.
[email protected]
E-mail:
During the
the last
last decades,
decades, the
the literature
literaature has
has been
been enriched
enriched with
with a number
number of proline-rich
proline-rich
During
homodeetic cyclopeptide
cyyclope
p pptide showing
showingg a significant
siggnificant
n biological
biologi
g cal disagreement
disaggreement between
between the
the
homodetic
cytotoxiicities displayed
displayyed by the
the natural
nattural peptides
peptides and
annd the
thhe corresponding
corresponding synthetic
synthe
h tic
cytotoxicities
counterppaart
r s. Two
Two main
main hypotheses
hypotheeses have
haavve been
been suggested
suggested to
to explain
explain this
this surprising
surprising
counterparts.
behaavvior: a minor
minor impurity,
impurity, only
only biologically
biologically detectable,
detectable, responsible
responsible for
foor the
the
behavior:
anntiproliferaative activity;
activity; or conformational
confform
o ational differences
differences due
duue to
to the
the presence
presence of a high
h gh
hi
antiproliferative
percentage
percentage off proline
proline moieties
moieties in
in a constrained
constrained macrocycle.
macrocycle.
Posters Session 2
Phaakkellistatins ssuffer
ufffer severely
severely ffrom
rom
o this
this phenomenon.
phenomenon. Herein
Here
r in w
nvestigaate tthe
he
h eeffect
ffect
Phakellistatins
wee iinvestigate
the proline
p ine replacement
prol
replacement by a pseudo-proline
pseudo-proline derived
derived from
from
r
the cysteine
cysteine which
which has
has
of the
the
been described
described to
to notably
notabl
b y enhance
enhannce the
the cis
cis geometry
geometry at
at the
the prolyl
p yl peptide
prol
peptide bonds.
bonds. In order
orrder
been
to shed
shed a bit
bit of light
light on tthis
hi
h s iissue,
ssuee, a llibrary
ibraarry of Cys
e,M
Mepro)-containing an
naloggs of
to
Cys(( M
Me,Mepro)-containing
analogs
Phaakkellistatin 19 ha
en ssynthesized,
ynthesized, bi
ologically ttested
ested aan
nd sstudied
tudied by N
MR.
Phakellistatin
hass be
been
biologically
and
NMR.
203
P 139
Posters Session 2
BACTERIAL CHARACTERIZATION BY REP_PCR TO GUARANTEE A
UNIQUE MICROBIAL LIBRARY AT PHARMAMAR.
Ana Peñalver, Carmen Schleissner, Paz Zúñiga, Beatriz Delgado, Carmen Cuevas
Microbiology R&D Dpt. PharmaMar SAU. Av. La Mina, 1, Es-28770, Colmenar Viejo, (Madrid). Spain
Efficient exploitation of the chemical diversity of marine microorganisms relies on
accurate genomic intraspecific dereplication in order to identify repeat strains.
Horizontal gene transference means that differentiation is required at the
subspecie/individual strain level. With the exception of some “predicable species”
(vertical transference), partial 16S rRNA sequencing is not efficient enough to be
applied upfront as a selection criteria.
Of the diverse molecular fingerprinting methods available, Repetitive sequence-based
PCR (REP-PCR) has been chosen as the most suitable for drug discovery from marine
derived bacteria at PharmaMar. Cost-effective, reproducible and discriminatory, this
protocol is based on the analysis and comparison of the individual patterns of DNA
bands generated after PCR with interspersed repetitive sequences. Specifically, (GTG)5
and ERIC2 are the primers used for filamentous and unicellular-morphology
actinobacteria respectively. Amplicons of different sizes, separated by electrophoresis,
allow us to establish the different patterns of DNA fingerprints specific for each strain.
The patterns of DNA fingerprints of each strain isolated from the same expedition are
compared to each other and the ratio of similarity between them estimated using the
BioNumerics software. Only one strain from each DNA fingerprint pattern is preserved.
As proof of concept, 23 different strains belonging to the same specie Streptomyces
antibioticus were analyzed. All the strains were cultured under the same conditions and
different pattern of biological activities and metabolites have been identified.
Posters Session 2
This method has enabled us to create a unique collection of marine microorganisms, as
the starting point for drug discovery to find potential producers of new antitumor
compounds.
204
Posters Session 2
P 140
BACTERIAL
BAC
CTERIAL ROMIDEPSI
ROMIDEPSIN
IN ISOLATED AT PHAR
PHARMAMAR
RMAMAR FROM THE
M
Ch
C
helidonura varians
MARINE MOLLUSC
Chelidonura
Mart
ta Pérez
z,, Carlos Urda,
Urdaa,, Rog
Rogelio
gelio Fernández
Fernández,
z,, Carlos dde Eguilior, Santiago
Marta
Pérez,
Buenoo and Carmen Cuevas
R&D
R&
D Area,
Area, PharmaMar
PharmaMar S.A.U.,
S.A.U., P.
P. I.
I. L
Laa Mina
Mina Norte,
Norte
t , Avda
Avda de
de los
los Reyes
Reyes 1, 28770
28770-Colmenar
-Colmenar Viejo
Viejo (Madrid),
(Madrid),
Sp
ain.
Spain.
E-m
mail: mp
erez@pharma
m mar.com
E-mail:
[email protected]
Posters Session 2
Althouggh the
Although
the ocean
oceann is
is home
home to
to the
the largest
larrgest diversity
diversity of
o major
major plant,
plannt, animal,
annimal, and
annd
microbial
Earth,
many
organisms
remain
undiscovered
m
icrobial groups on E
arrth, m
anny of tthese
hese organ
nisms re
main un
discovered aand
nnd
unc
lassified. M
arine iinvertebrates
nvertebrates aare
rre know
rbour di
verse ccommunities
ommunities of
unclassified.
Marine
knownn ttoo har
harbour
diverse
microorganisms,
which
often
with
hosts.
m
icroorrgaannisms, w
hich of
ften fform
orm
o m sstable
tabble aand
nd sspecific
pecific aassociations
ssocciations w
ith ttheir
heir hos
ts.1 T
The
he
role
role off these
these diverse
diverse microorganisms
microorrgannisms in
in marine
marrine molluscs
mol
o luscs varies
vaarries from
frrom simple
simpl
pe
colonizaattion to
to mutualistic
mutualistic symbiosis.
symbi
b osis. In some
some cases,
cases, associated
associatted bacteria
bacteria can
can supply
suppply
colonization
compouunds with
with antibiotic,
antibiotic, antifungal
anntifunga
u l or cytotoxic
cytotoxic activities
activities for
for
o defence.
defence.
compounds
Herein,
wee re
report
romidepsin
(trade
name
Herein, w
port tthe
he iisolation
solation of rom
idepsin (t
trrade na
ame IIstodax
stodax®) ffrom
rom
r
a ccrude
rude eextract
xttract
the marine
marrine mollusc
mollusc Chelidonura
Chelidonurra vvarians
arians ccollected
ollected of
ff tthe
h ccoast
he
oast of M
esali (T
annzannia).
of the
off
Mesali
(Tanzania).
marine
n aquaria
aquaarria this
this cephalaspidean
cephalaspiidean is
is sometimes
sometimes used
used to
to get
get rid
rid of flatworms
flatworms which
whi
h ch
In marine
offten live
live
v on corals
corals and
and
n can
cann starve
starrvve the
the corals
corals to
to death
death byy competing
com
o ppetingg for
for
o their
the
h ir planktonic
pplannktonic
o
often
food.
o
Roomidepsin is
is a biciclyc
biciclyc depsipeptide
d psipeptide that
de
thhat produces
produces an
an antineoplastic
anntineoplastic effect
effect via
via
food.
Romidepsin
inhibition
o of hi
stone de
acetylase,
e aand
nnd w
as ori
ginally ob
btained ffrom
rom
r
ccultures
ultures of tthe
he
inhibition
histone
deacetylase,
was
originally
obtained
terrestrial --proteobacteria
proteobacteria Chr
o obacterium vviolaceum,
om
iolaceum
m, a known microorganism
microorgaannism
terrestrial
Chromobacterium
relatted ttoo quorum
m sensing
sensing signalling
signalling through
through the
the production
productionn off violacein.
violacein.
related
The true
truee origin
origin of the
the romidepsin
romidepsin in
in the
the marine
marrine mollusc
mollusc remains
reemains unclear.
unclearr. Since
Since marine
mari
r ne
The
molluscs are
are
r known
known to
to harbour
harrbour marine
marrine bacteria,
bacteria, the
the true
true source
sourc
o e of the
the romidepsin
romidepsin could
coul
o d
molluscs
be aann aas-yet
unidentified
marine
with
mollusc
s yet uni
sdentified m
arrine ba
bbacteria
cteria aassociated
ssociated w
ith tthe
h m
he
ollusc or aalternatively
lternattively tthe
he
mollusc may
may have
havve sequestrated
sequestraated the
the romidepsin
romidepsin from
from
r
its prey,
p y,2 or even
pre
even be responsible
responssible
mollusc
its
itself
biosynthesis.
itself for
for
or romidepsin
romidepsin bi
osynthesis.
R
eferences
References
1.
2.
a El
a)
Elshahawi,
shahawi, S.
S. I.;
I.; Trindade-Silva,
Trindade-S
Silva, A.
A. E.;
E.; Hanora,
Hanora, A.;
A.; Han,
Han, A.W.;
A.W.; Flores,
Flores, M.
M. S.;
S.; Vizzoni,
Vizzoni, V.;
V.;
Sc
S
hrago, C.
C. G.;
G.; Soares,
Soares, C.
C. A.;
A.; Concepcion,
Concepcion, G.
G. P.;
P.; Distel,
Distel, D. L.;
L.; S
c h m id t, E
nd H
aygood,
Schrago,
Schmidt,
E.. W
W.. aand
Haygood,
M G. Pr
M.
oc N
atl Ac
ad SSci
ci U S A
110(4), 295-304. b)
b) Kahalalide-producing
Kahalalide-producing bacteria,
bacteria,
Proc
Natl
Acad
A.. 2013, 110(4),
W 2005042720A 2.
WO
WO2005042720A2.
S
Sl
attery, M.;
M .; A
v ila , C
.; St
armer, JJ.;
.; aand
nd Paul,
Paul, V.
V. J.
J. Journal
Journal off E
xpperimental Marine
Mar
a ine B
iologyy and
Slattery,
Avila,
C.;
Starmer,
Experimental
Biology
E
Ec
ology, 1998, 226
3-49.
Ecology,
226,, 333-49
Acknowkedgements
A
cknow
wkedgements
•
•
Mr
M
Mr.. P
P.. JJ.. R
Ruysenaars
uysenaars (The
(The Pemba
Pemba
b cchannel
hannel fishing
fishing cclub
lub S
Shimoni).
himonni).
M
Mi
nistry ooff L
ivestock aand
nd F
is h e rie s D
evelopment. F
isheries D
epartment (Republic
(Republic of
of Tanzania).
Tanzania).
Ministry
Livestock
Fisheries
Development.
Fisheries
Department
205
P 141
Posters Session 2
BRIDGED TRICYCLIC SESQUITERPENES FROM THE TUBERCLE
NUDIBRANCH Phyllidia coelestis
Anuchit Plubrukarn, Sunan Jaisamut
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince
of Songkla University, 90112, Songkhla, Thailand.
Posters Session 2
Nudibranchs have been long known to be capable of sequestering toxic metabolites
from their prey, including sponges and corals, and convert such metabolites for their
own chemical defense. The chemical investigation in a Thai specimen of the tubercle
nudibranch Phyllidia coelestris led to the isolation of a new bridged tricyclic
sesquiterpene,
1-formamido-abeo-pupukeanane
(1),
along
with
2formamidopupukeanane, which is reported here as a natural product for the first time.
The tricyclo[5.3.0.03,8]decane skeleton of 1 is unprecedented, and the rearrangement
toward the sponge-related pupukeanane skeletons is proposed here.
206
Posters Session 2
P 142
ORAL TOXICITY AND HISTOPATHOLOGICAL ASPECTS OF
Pseudoanabaena galeata AND Geitlerinema splendidum (CYANOBACTERIA,
CYANOPHYCEAE) EXTRACTS ADMINISTRATED IN MICE
Marisa Rangel1, Joyce C.g. Martins1, Angelica N. Garcia2, Geanne A.a. Conserva2,
Adriana C. Neves2, Celia L. Santanna2, Luciana R. Carvalho2
1
Butantan Institute, Av. Vital Brasil 1500, 05503-900, Sao Paulo, Brazil.
2
Botanic Institute, Phycology Section, Sao Paulo, Brazil.
Toxic cyanobacteria are commonly found in drinking water supplies and are responsible
for numerous cases of humans’ envenomations in Brazil. P. galeata and G. splendidum
are examples of toxic species very frequently found in Sao Paulo´s reservoirs, the most
densely populated area in Brazil.
During the search for bioactive substances from strains maintained in the Cyanobacteria
Culture Collection of the Institute of Botany, Sao Paulo, Brazil, the acetic acid extracts
(AE) of CCIBt-3082 - P. galeata and CCIBt-3223 - G. splendidum showed toxicity in
mouse bioassay (v.o.).
P. galeata AE didn’t cause deaths at a 1 g.kg-1, but induced symptoms: eyebrow ptosis,
straub tail and pain. After one week the euthanized animals presented hemorrhage in the
liver. Histology showed: disorganization of the hepatic parenchyma, necrosis, loss of
vein endothelium, hyperemia; alterations in the kidneys’ convoluted tubules; lungs were
unaffected. G. splendidum AE induced dyspnea, paralysis and pain at 0.5, 1 and 2 g.kg-1
doses, and one death at 0.5 g.kg-1. Necropsy of euthanized mice showed hemorrhage in
the lungs, kidneys and liver. The lungs presented hemorrhagic focuses, edema, alveolar
collapse and hyperplasia (macrophages). Damage in kidneys and liver were similar to P.
galeata extract administration, but inflammatory cells were also observed.
Further analysis of both extracts indicated absence of microcystins and saxitoxins,
absence of haemolytic activity, and presence of two unknown anti-AChE substances in
G. splendidum AE. Thus, P. galeata and G. splendidum are producers of new toxins that
affect mammals when administrated orally.
Acknowlegements
Posters Session 2
FAPESP, CNPq
207
P 143
Posters Session 2
CHEMICAL ECOLOGY OF MARINE SPONGES AND THE DISCOVERY OF
NEW DRUGS
Diana C. Restrepo E.1,2, Mario H. Londoño M.1,3
2
1
Universidad de Antioquia, Medellín, Colombia;
Research group of Marine Natural Products, Faculty of Pharmaceutical Chemistry; 3Research group of
Limnobase y Biotamar Institute of Biology, Faculty of Exact and Natural Sciences.
Posters Session 2
Marine organisms are being studied for finding compounds with uses on different fields
(medicine, nutrition, engineering). They have been recognized as new drugs being
source of bioactive compounds with biomedical and pharmacological activities.
However, only few marine species have been studied; the presence or production of
those metabolites in marine organisms is apparently related to evolutionary pressures
occurred inside the ecosystems. Additionally, it seems to have importance in adaptive
processes, such as a chemical mechanism (defensives and predation) for preventing
infections by pathogens, invertebrate’s settlement, or for avoiding being eaten or
removed. Marine sponges are consumed by mollusks, crustaceans, echinoderms, fish
and turtles. In addition, sponges are important as microhabitats of bacteria, algae and
other invertebrates, with camouflage strategies. The purpose of this investigation is
finding a possible ecological and pharmacological function connection in terms of
compounds identified in marine sponges. A literature-based review and the analysis
about both processes were made. As a result, the ecological processes could be related
to the production of identified compounds as metabolite sources with important
biological activities, as immunodulatory, antifungical, antitumor, anti-inflammatory,
antimalarial, antiviral, and others. Additionally, though more than 5500 metabolites
have been reported since 1950, and that the marine ecological chemistry has matured
during the last two decades, the interest in developing biological studies to discover
roles of those metabolites is still poor. Therefore, ecological studies for knowing
physiology of marine organisms associated to their defense, predation or nutrition
mechanisms with other potential applications that support current investigations, is
deeply needed.
208
Posters Session 2
P 144
FUNDACIÓN MEDINA’S NATURAL PRODUCTS COLLECTION: INTEGRATED
SOLUTION FOR INNOVATIVE MARINE DRUG DISCOVERY
José R. Tormo, Catalina Moreno, Francisca Muñoz, Daniel Oves-Costales, Ignacio
González, Víctor González-Menéndez, Mercedes de la Cruz, Maria Cândida Monteiro,
Noureddine El Aouad, Ignacio Pérez-Victoria, Jesús Martín, Francisca Vicente, Olga
Genilloud and Fernando Reyes
Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía,
Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 3,18016-Granada, Spain.
Posters Session 2
Based on more than fifty years of cumulative experience in the pharmaceutical industry and
a worldwide collaboration with more than 20 partners, Fundación MEDINA is creating,
improving and characterizing a high quality collection of natural product extracts and
fractions for HTS drug discovery from marine-derived microorganisms. This precious
resource will be open to worldwide collaborative discovery initiatives focused on novel
therapeutic approaches and clinical development of medicinal agents.
Fundación MEDINA offers an integrated solution for natural products discovery derived
from a superbly diverse, laboratory-optimized and well maintained microbiological arsenal
resulting in a collection thoroughly annotated with chemical and biological data.
MEDINA’s Natural Products Collection of 7000 samples will cover an uncommonly
unexplored broad chemical space resulting from a variety of fermentation products.
Innovative semi-automated methodologies for SPE extraction and fractionation techniques
have been integrated with the generation of this specific collection by using:
• Marine-derived actinomycetes and fungi as source of secondary metabolites
• Four fermentation media to ensure a diversity of secondary metabolite production
• SPE extraction protocols to remove salts from culture media
• Chromatography on highly retentive resins and reversed-phase separations
• Automated procedures for the generation of a HTS compatible collection
• Chemical & Biological profiling emphasizing its anti-infective properties and
chemical space.
209
P 145
Posters Session 2
HALOPHYTE NATURAL EXTRACTS WITH POTENTIAL USE IN TUMOR
PREVENTION AND TREATMENT
Maria João Rodrigues, Luisa Custódio, Luísa Barreira, Catarina Vizetto-Duarte,
João Varela
Centre of Marine Sciences, Universidade do Algarve - Campus de Gambelas, Ed. 7, 8005-139, Faro,
Portugal.
We screened the antioxidant, anti-inflammatory and cytotoxic properties of different
extracts of five halophytes species from the southern Portugal, namely Arthrocnemum
macrostachyum, Plantago coronopus, Juncus acutus, Carpobrotus edulis and Atriplex
halimus. Radical scavenging activity (RSA) was evaluated against 1,1-diphenyl-2picrylhydrazyl (DPPH) and 2,2"-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)
(ABTS) radicals. Total phenolic content (TPC) was assessed by the Folin-Ciocalteau (FC) assay. Anti-inflammatory activity was determined through the inhibition of nitric
oxide (NO) production by lipopolysaccharide (LPS)-stimulated macrophages by the
Griess method. The cytotoxicity of the extracts against HepG2 and THP1 cells was
estimated by the [(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]
(MTT) assay, and the results were compared with the S17 non-tumor cells. Induction of
apoptosis was assessed by 4",6-diamidino-2-phenylindole (DAPI) staining. The highest
RSA was observed in C. edulis methanol and the J. acutus ether extracts against the
DPPH•; and J. acutus ether and A. halimus ether extracts against the ABTS•+. Methanol
extracts of C. edulis and P. coronopus, and the ether extract of J. acutus had the highest
TPC. The A. halimus chloroform and P. coronopus hexane extracts displayed antiinflammatory activity. The ether extract of J. acutus selectively reduced the viability of
HepG2 cells, with a selectivity index (SI) of 7.4, when compared with non-tumor cells.
Cell death was associated with apoptosis.
Posters Session 2
This work was supported by SEABIOMED (PTDC/MAR/103957/2008) and XtremeBio (PTDC/MAREST/4346/2012) projects funded by Foundation for Science and Technology (FCT) and Portuguese
National Budget. Luísa Custódio and Catarina Vizetto-Duarte acknowledge a FCT post-doctoral research
fellow (SFRH/BPD/65116/2009) and a PhD grant (SFRH/BD/81425/2011), respectively.
210
Posters Session 2
P 146
THELEPAMIDE:
TH
E
ELEP
AMIDE: AN
AN UNPRECEDENTED
UNPRECEDENTED CYTOTOXIC
CYTOTO
T XIC PEPTIDE
PEPTIDE FROM
FROM
TH
EP
OLYCHAETE A
NNELID T
Th
heleppus ccrispus
rispu
p s
THE
POLYCHAETE
ANNELID
Thelepus
Jai
ime Rodr
ígu
g ez1, Car
Carlos
loos Jiménez
Jiiménez1, Ros
Rosaa M.
M. Nieto
Nieto1, María
Mar
a ía Blanco
Bllaanco1, Phillip
Phillip Cr
Crews
ews
w2
Jaime
Rodríguez
1
Universidad ddee A C
Universidad
Coruña,
oruña, Departamento
Departamento de
de Química
Química Fundamental,
Fundamental, Facultad
Facultad de
de Ciencias,
Ciencias, Campus
Campus da
da
Zapateira, 15071, A Coruña,
Coruña, Spain.
Spain. 2Un
Univeristy
iveristy ooff C
California
a lif o r n ia S
Santa
a n ta C
Cruz,
ru z, S
Santa
a n ta C
Cruz,
ruz, 995064,
5064, US
USA.
A
A.
Zapateira,
E-m
mail: ja
im e .r o d r ig u e z @ u d c .e s
E-mail:
[email protected]
Marine
organisms
have
provenn ttoo produc
producee aann va
vast
variety
biologically
M
arine organ
nisms ha
avve prove
st var
riety of
o cchemically
hemically aand
nnd bi
ologically
ssignificant
ignificannt secondary
secondaarry metabolites.
metabbolites. The
The phyla
phyla Annelida
Annelida and
annd Hemichordata
Hemichordaata (marine
(mari
r ne
worms)
w
orms) have
havve had
had several
several prior
pprior chemical
che
h mical examinations.
exaaminattions. These
Theese studies
studies involved
involved isolation
isolation
disteroidal
(cephalostatins),
of bromophenols,
brom
mophenols, halogenated
halogenaated iindoles,
n es, cchlorines,
ndol
hlorines, di
steroida
d l aalkaloids
lkaloids (c
ephalostatins),
ortho-antraquinones,
ort
ho-anntraquinones, and
and
n polypeptides
polypeeptides which
which have
haave
v shown
show
wn interesting
interesting activities.
activities. The
The
Thelepus
was
because
ssand-encrusted
and-enccrusted marine
mari
r ne worm
worm T
he
heleppus ccrispus
rispus
p w
as selected
selected ffor
or
o sstudy
tudy be
cauuse iits
ts ttotal
otal
polar
po
lar extract
ext
x ract showed
showed selective
selective activity
activity against
against leukemia
leukemia tumor
tuumor cells
cells (ED
(ED50< 5μg/mL).
5μg/mL).
Therefore
Therefore the
the methanolic
methannolic extract
extract was
was partitioned
partitioned with
with hexanes,
hexan
x nes, followed
fol
o lowed by methylene
methyl
h lene
chloridee and
annd MeOH/H
MeOH/H2O giving
givingg a final
final extract
extract which
which also
also showed
showed same
sam
me selective
selective
chloride
cytotoxicity
cytotoxiicity against
against CCRF-CE leukemia
leukemia cells
cells (IC50< 55μg/mL).
μg/mL). Purification
Purification by gel
gel
permeation on S
ephadex L
H-200 w
ith M
eOH w
as bi
oaassay-guided ffurnishing
urni
u shing pure
p
permeation
Sephadex
LH-20
with
MeOH
was
bioassay-guided
thelepaamide (1)
(1) as
as an
an optically
optically active
active amorphous
amorphous solid.
solid.
d Their
The
h ir structure
structuure was
was deduced
deduced by
thelepamide
mass
mass spectrometry,
spe
p ctrometry, NMR
NMR means,
meanss, DFT
DFT molecular
molecularr modeling
modeling calculations,
calculations, and
and partial
paarrtial
chemical ssynthesis.
ynthesis. This
This compound
compoound has
has no precedent
precedent in
in the
the literature
literaature and
and can
can be
chemical
biosynthetically
acetate
biosynthe
h tically viewed
viewed from
from
r
acetate and
annd three
three different
different aminoacids,
aminoacids, cysteine,
cysteine,
isoleucine,
isoleucine
n , and
annd glycine.
glycine.
References
References
2
2.
3.
(a)
( ) Gribble,
(a
Gribble, G.
G. W.
W. J C
Chem
hem Educ
Educ 1994, 71,
71, 9907-911.
07-911. (b)
(b) Corgiat,
Corgiiat, J.
J. M.;
M.; Dobbs,
Dobbs, F.
F. C.;
C.; Burger,
Burger, M.
M.
W;S
W.
cheuer, P. J.
J. Comp
Comp Biochem
Biochem Physiol
Physiol 1993, 106B,
106B, 883-86.
3-86.
W.;
Scheuer,
P ttit, G
Pe
noue, M.;
M.; Kamano,
Kamano, Y.;
Y.; Dufresne,
Dufresne, C.;
C.; Christie,
Christie, N.;
N.; Niven,
Niven, M.
M. L.;
L.; Herald;
Herald; D.
D. L.
L. J.
J
Pettit,
G.. R
R;; IInoue,
C em SSoc.
Ch
oc. Ch
em. Co
mm. 1988,
1988, 8865-867,
65-867, Corrigendum
Corrigendum 1988, 11440.
440.
Chem
Chem.
Comm.
C mino, G.;
Ci
G.; De
De Rosa,
Rosa, S.;
S .; S
odano, G.
G. J. N
at. Pr
od. 1985, 48, 8828.
28.
Cimino,
Sodano,
Nat.
Prod.
Posters Session 2
1.
211
P 147
Posters Session 2
KILWASTEROLS,
K
ILW
WASTEROLS, N
NEW
EW C
CYTOTOXIC
YTOTOXIC P
POLYOXYGENATED
OLYOXYGENATED S
STEROIDS
TEROIDS
FROM D
Dy
ysidea ssp.
p.
Dysidea
Raqu
el Rodr
ígguezz---A
Acebess,, Car
Carlos
loos de Eguilior,
Eguiliorr, S
Santiago
antiago B
Bu
Bueno
eno and
and Carmen
Carmen Cuevas
Cuevas
Raquel
Rodríguez-Acebes,
R&D
R&
D Area,
Area, PharmaMar
PharmaMar S.A.U.,
S.A.U., P.
P. I.
I. La
La Mina
Mina N
Norte,
orte, A
Avda
vda de
de los
los Reyes
Reyes 1,
1, 28770-Colmenar
28770-Colmenar Viejo
V ie jo
(Madrid), Spain.
S p a in .
(Madrid),
E-mail: rro
[email protected]
E-mail:
[email protected]
Posters Session 2
marine
wee ha
In our continuing
continuing eefforts
ffort
o s to
to isolate
isolate aanticancer
nnticancer ccompounds
ompounds ffrom
rrom m
ari
r ne ssources,
ources, w
hhave
ave
v
iinvestigated
nvestigated the
the cchemical
hemical ccomposition
omposition of a sample
sample of D
ysidea ssp.,
p.
p , collected
collected iinn K
ilwa,
Dysidea
Kilwa,
ne
ar the
thee T
anzannian ccoast
oast iinn 200
05. As
As a result
result of this
this study
study
u y we
we have
havve discovered
discovered the
the
near
Tanzanian
2005.
ki
lwasterols, a new
new family
family of polyoxygenated
polyoxygenaated steroidal
steroidaal terpenes
terpenes with
with an
an unusual
unussual
kilwasterols,
ssubstitution
ubstituttion pattern.
paattern.
U
sually steroids
steroids bear
bear a ge
m-dimethyl group or two
two hydrogens
hydroggens at
at the
the C4 carbon,
carrbon, and
anndd the
the
Usually
gem-dimethyl
pre
sence of onl
ethyl grou
up aatt tthis
his pos
ition, aass ffound
ound
o d iin
n tthe
he ki
lwasterols, ha
oonly
y
presence
onlyy one m
methyl
group
position,
kilwasterols,
hass onl
been
reported
redd aalgae.
be
en re
p ed a ffew
port
ew ttimes
imes ffrom
rom
r
ssamples
amples off ffungi
ungi
u
or re
lgaae.1
In tthis
his w
ork w
scribe tthe
he iisolation
solat
ation aand
nnd sstructural
tructural de
term
minattion of tthis
his ne
w ffamily
amily of
work
wee de
describe
determination
new
ccompounds,
ompouunds, aass w
ell aass da
ta ffrom
rom
r
iinn vvitro
itro cytotoxicity
cytotoxicity aassays.
ssayys
y.
well
data
References
R
eferences
1.
(a
(a)) Batta
Batta et aal,J.
l,J. C
Chem.
hem. Soc.,
Soc., Perkin
Perkin Trans.
Trans. 1 1975,
1975, 4451-455.
51-455. (b)
(b) Hai
Hai et aal,
l, Phytochemistry
Phhytochemistry 1996,
1
4 1083-1084.
1083-1084. (c)
(c) Liu
Liu et aal,
l, Phytochemistry
Phytochemistrry 2009, 70,
Ph
70, 558-563.
558-563. (d)
(d) Wang
Wang et al,
al, Planta
Planta Med.
M ed .
41,
2
75, 1602-1607Horne,
1602-1607Horne, D. A. et al.
al. Org.
Orrg. Lett.
Lett. 2000, 2 (20),
(20), 33185.
185.
2009,
75,
Acknowkedgements
A
cknow
wkedgements
•
•
212
Mr
M
Mr.. P
P.. JJ.. R
Ruysenaars
uysenaars (The
(The Pemba
Pemba channel
channel fishing
fishing club
club Shimoni).
S h im o n i).
M
Mi
nistry ooff L
ivestock aand
nd F
isheeries D
evelopment. F
isheries D
epartment (Republic
(Republic of
of Tanzania).
Tanzannia).
Ministry
Livestock
Fisheries
Development.
Fisheries
Department
Posters Session 2
P 148
PURPUREADINS:
P
URPUREADINS: NEW
NEW ANTICANCER
ANTI
T CANCER COMPOUNDS
COMPOUN
NDS FROM
FROM THE
THE SPONGE
SPONGE
Psseudocerattina pu
P
rpu
p rea
Pseudoceratina
purpurea
Raqu
el Rodr
ígguezz---A
Acebes1, Rog
Rogelio
gelio Fe
Fernández
rnández1, Fe
Fernando
rnando
d Reyes
Reeyes2, M
Mªª José
José Guillén
Guillén1,
Raquel
Rodríguez-Acebes
1
1
1
Fernando
Fernando Asenjo
Asenjo , Car
Carlos
los
o dee Egu
Eguilior
ilior , S
Santiago
antiago Bu
Bueno
eno an
andd Carmen
Carmen Cuevas
Cuevas1
1
R&D
R&
DA
Area,
rea, P
PharmaMar
harmaMar S.A.U.,
S.A.U., Pol.
Pol. Ind.
Ind. La Mina
Mina Norte,
N o r te , A
Avda.
vda. D
Dee los
los Reyes,
Reyes, 1,
1, 28770-Colmenar
V ie jo
(Madrid), Spain.
Spain. 2Fu
Fundación
ndación Medina,
Medina, Avda.
Avda. del
del Conocimiento
Conocimiento 3;
3; Edificio
Edificio Centro
Centro de
de Desarrollo
D e s a rro llo
(Madrid),
Fa
armacéutico. Parque
Parque Tecnológico
Tecnológico de
de Ciencias
Ciencias ddee la
la Sa
lud. 180
16, A
rmilla, G
ra n a d a , S
pain
Farmacéutico.
Salud.
18016,
Armilla,
Granada,
Spain
Email: rro
[email protected]
E-mail:
[email protected]
Posters Session 2
Marine ssponges
Marine
ponges be
belonging
longing ttoo tthe
he orde
orderr V
Verongida
erongida aare
re
r w
well-known
ell-known ffor
or
o produc
producing
ing a llarge
arge
va
arriety of brominated
brominaated tyrosine
tyrosine metabolites.
metabolites.1 For
For this
thhis reason,
reason, these
these ccompounds
ompounds ha
hhave
avve
variety
been
potential
markers
Verongida
been cconsidered
onnsidered aass pot
ential cchemotaxonomic
hemotaxonomic m
arke
r rs of V
erongida ssponges.
ponges.2 A wide
wide
range
n
o biological
biological activities
activities have
havve been
ha
been reported
reported for
for
o these
these compounds,
compounds, including
includding
range
of
anntimicrobi
r al, anti-enzymatic,
annti-enzymatic, cytotoxic
cyttotoxic aand
nnd antiparasitic
anntiparrasitic aactivities.
ctivities.3
antimicrobial,
Chemical sstudy
tudy of a sample
sam
mple of P
seudoceratina pur
rpur
p ea,
a collected
collected of
ff the
the ccoast
oast of
Chemical
Pseudoceratina
purpurea,
off
Bunaken,
n N
orthern Indone
sia, led
led us to
to the
the discovery
discoveryy of two
two new
new compounds,
compounnds,
Bunaken,
Northern
Indonesia,
purpureadin A aand
nd B, w
ith a uni
q ffused
que
us
u ed -lactamoxazolidine ccore
ore tthat
hatt ha
never been
b en
be
purpureadin
with
unique
-lactam-oxazolidine
hass never
previoussly described.
described. The
The chemical
chemical structure
strructure and
annd the
thhe relative
relattive stereochemistry
stereochemistry off all
all
previously
three cchiral
h ral ccentres
hi
entres ha
ve be
en una
ambiguously aassigned
ssigneed us
ing 1D aand
nnd 2D
-NMR
three
have
been
unambiguously
using
2D-NMR
techniques.
techniquues.
Purpureadins
have
Purpureadins A and
annd B ha
ve in
in vitro
vitro cytotoxic
cytotoxic actitivities
actitivities in
in the
the micromolar
micromolarr range
raannge
against various
vaari
r ous human
humann cancer
cancer cell
ceell lines.
lines. A program
prograam of in
in vivo
vivo experiments
experiments is being
beeing
against
conducted with
with these
these molecules.
molecules.
conducted
References
References
1.
2.
3.
Kochanowska
K chanowska et aal.,
Ko
l., J. Nat.
N a t. P
Prod.
rod. 2008, 71,
71, 1186-189.
86-189.
(a)
Prod.
( ) Ciminiello
(a
Ciminiello et al.,
al., J.
J. Nat.
Nat. P
rod. 1999, 62,
62, 590-593.
590-593. (b)
(b) Ciminiello
Ciminiello et al.,
al., J.
J. Nat.
Nat. Prod.
Prod. 2000,
20000,
63,
6 , 2263-266.
63
63-266.
( ) Xu
(a
Xu et al.,
al., Bioorg.
Bioorg. Med.
Med. Chem.
Chem. Lett.
Lett. 2011, 21,
21, 846-848.
846-848. (b)
(b) Shaker
Shaker et al.,
al., Chem.
Chem. Biodivers.
B io d iv e r s .
(a)
2
7, 22880-2887.
880-2887. (c)
(c) Buchanan
Buchana
n n et al., J. Nat.
Nat. Prod.
Prod. 2009, 72,
7 , 973-975.
72
973-975.
2010,
7,
Acknowkedgements
A
cknow
wkedgements
•
•
•
•
Sa
S
Sam
m Ratulangi
Ratulangi University
University ooff Manado.
Manado. Indonesia.
Indonesia.
U
Un
iversitá Politecnica
Politecnica ddelle
e lle M
arche Ancona.
Ancona. Italy.
Italy.
Universitá
Marche
Ministry
Marine
Affairs
Fisheries.
M
Mi
nistry ooff Ma
rin e A
ffairs aand
nd F
isheries. Republic
Republic of
of Indonesia.
In d o n e s ia .
D
Dr
osé L
uis C
arballo C
enizo ((University
University of Me
xico, IInstituto
nstituto ddee C
ie n c ia y L
im n o lo g ía ).
Dr.. JJosé
Luis
Carballo
Cenizo
Mexico,
Ciencia
Limnología).
213
P 149
Posters Session 2
STELLATOLIDES:
S
TEL
LLATOLIDES: NEW
NEW ANTICANCER
ANTICANCER
R PEPTIDES
PEPTIDES
E FROM
FROM THE
THE SPONGE
SPONGE
E
cionemia acervus
acervus
Ecionemia
Raqu
uel Rodr
ígguez--A
Acebes1, Fernando
Feernando Reyes
Reeyes2, S
Simon
imon M
Munt
unt1, Car
Carlos
loos de Eguilior
Eguilior1,
Raquel
Rodríguez-Acebes
1
1
Santiago
Bueno
S
antiago
a Bu
eno an
andd Carmen
Carmen Cuevas
Cuevas
1
Department
De
partment of Medicinal
Medicinal Chemistry,
Chemistry,, PharmaMar
PharmaMar S
S.A.U.,
.A .U ., P
P.. II.. L
Laa M
Mina
ina Norte,
Norte, A
Avda
vda de los
los Reyes
Reyes 1,
Viejo (Madrid),
(Madrid), Spain.
Spain. 2Fu
Fundación
ndación MEDINA,
MEDINA, Avda.
Avda. del
del Conocimiento
Conocimiento 3;
3; Edificio
Edificio
28770-Colmenar
Ce
ntro de
de Desarrollo
Desarrollo Farmacéutico.
Farmacéutico. Parque
Parque Tecnológico
Tecnológico de
de Ciencias
Ciencias de
de la
la Salud.
Salud. 18016,
18016, Armilla,
Armilla,
Centro
Gr
anada, Spain.
S p a in .
Granada,
Email: rro
[email protected]
E-mail:
[email protected]
Posters Session 2
Cyc
lic de
ddepsipeptides
psipeptides have
have emerged
emergged as
as a very
very important
importannt class
class of bioactive
bioactive compounds
compouunds
Cyclic
ffrom
rom
r
marrine organisms.
orgaannisms. Several
Severa
r l of these
these molecules,
molecules, such
such as
as callipeltins
callipeltins1 and
and
marine
paappuaamides,2 ha
have
ve been
been described
described as
as cytotoxic,
cytotoxic, antiviral
antiviral and/or
annd/
n or antifungal
anntifunga
u l compounds.
compoundds.
papuamides,
As part
marine
parrt of our continuing
continuing efforts
effort
o s to
to isolate
isolate anticancer
annticanncer ccompounds
om
mpounds ffrom
rom
r
m
arrine ssources,
ourrces,
we have
haavvee isolated
isolated a new
new class
class of cyclic
cyclic depsipeptides
depsipeptides with
with micromolar
micromolarr to
to submicromolar
submicromolarr
we
in vitro
vitro cytotoxic
cytotoxic activities,
activities, from
frrom the
the sponge
sponge Ecionemia
Ecionemia acervus.
acervus. Six
Six structures
strructure
u s
in
belonging
n ttoo a ne
w ffamily
am
amily of compounds,
com
o pounds, given
given the
the ge
n ral nam
ne
me sstellatolides,
tellatolides, ha
hhave
ave
v
belonging
new
general
name
been characterized
cha
h racterized aalong
long w
ith an
an open-chain
open-chain analogue,
annalogue, of which
which two
two representative
representative
been
with
examples
exaamples are
are shown
shown below.
below. The
Thee sequence
sequence and
and stereochemistry
stereochemistry of all
all the
the aminoacids
am
minoacids
present
present in
in these
thhese molecules
molecules has
has been
b en established
be
estabblished using
using a combination
combination of spectroscopic
spectroscopi
o c
analysis,
annalysis, chemical
chemical degradation
degradaation and
aannd derivatization
derivaatization studies.
studies.
s Furthermore,
Furthermore, the
the complete
compl
p ete
structure
hass be
been
structuree of stellatolide
stellatolide A ha
een cconfirmed
onffirmed by ttotal
otal ssynthesis
y thhesis aand
ynt
nnd tthis
his will aalso
lso be
presented
presented iinn tthis
his ssymposium.
ymposium.
This
This discovery
discovery has
has given
given rise
rise to
to a new
new patent
patent application
appl
p ication3 aand
nnd a pre
preclinical
clinical progra
program
am of
iinn vivo
vivo experiments.
experiments.
References
R
efe
f rences
1.
2.
3.
Z
Za
Zampella
mpella et aal.,
l., J. A
Am.
m. Chem.
Chem. Soc.
Soc. 1996, 118,
118, 66202-6209.
202-6209. (b)
(b) Zampella
Zampella et aal.,
l., Tetrahedron
Tetrahedron
L tters, 2002, 43,
Le
43, 66163-6166.
163-6166. (c)
(c) D’Auria
D’Auria et al.,
al., Tetrahedron,
Tetrahedron, 1996, 52,
52, 99589-9596.
589-9596.
Letters,
F rd et aal.,
Fo
l., J. A
m. Ch
em. Soc.
Soc. 1999,
1
121, 55899-5909.
899-5909.
Ford
Am.
Chem.
121,
R
Ro
dríguez, R.;
R.; F
ernández, R.
yes, J.F.;
J.F.; Martín,
Martín, M.J.;
M.J.; Marco,
Marco, I.;
I.; D
igón, I.;
I.; Francesch,
Francesch, A.;
A .;
Rodríguez,
Fernández,
R.;; Re
Reyes,
Digón,
C evas, M.C.
Cu
M.C. Stellatolide
Stellatolide analogs
analogs as
as anticancer
anticancer ccompounds.
ompounds. Int.
Int. Appl.
Appl. Pat.
P a t. W
O 22010/007147
0 1 0 /0 0 7 1 4 7
Cuevas,
WO
A , 20
A1
20 January
January 2010.
2010.
A1,
A
cknow
wledgements
Acknowledgements
•
•
•
214
Dr
D
Dr.. E
Edouard
douard Mara.
Mara. Institut
Institut H
Halieutique
alieutique et
et de
de Sciencies
Sciencies Marines
Marines IH.
IH. SM Université
Université de
de Toliara.
T o lia ra .
M
Mi
nistère ddee L
’agriculture de
de L’elevage
L’elevage et
et de
de la
la Peche.
Peche. Madagascar.
Madagascar.
Ministère
L’agriculture
D
Dr
osé Lu
is C
a r b a llo C
enizo (University
(University of
of M
exico, IInstituto
nstituto ddee C
iencia y Limnología).
Limnología).
Dr.. JJosé
Luis
Carballo
Cenizo
Mexico,
Ciencia
Posters Session 2
P 150
EVALUATION OF SEA CUCUMBER FROM YUCATAN MEXICO AS A
SOURCE OF ANTIPROTOZOAL AGENTS
Sergio Rodriguez-Morales1, Rosi Moo Puc2, Daniel Chavez-Velasco3
1
Unidad De Química Sisal, Fac. Quimica Unam, Av. Colón No. 503 F X Calle 62 Y Calle 72 O Reforma.
Col. Centro. Cp 97000, Mérida,Mexico. Yucatán, Invoice Address Av. Universidad No 3000 Col UNAM,
Cu, Cp04510, Del Coyoacan Mexico D.f., 04510, Merida , México. 2 Inst Mexicano Seguro Social
Unidad Invest. Med. Yucatan, Unidad Med Alta Especialidad, Merida, Yucatan, Mexico. 3 Inst
Tecnologico De Tijuana Centro De Graduados E Investigación, Tijuana, Baja California Norte, Mexico
Amitocondrial protozoan parasites: Giardia intestinalis, Entamoeba histolytica and
Trichomonas vaginalis, affect more than a one third of the worldwide population. Drug
therapy alternatives presents drawbacks like side effect and lately resistance, and the
problem is aggravated because the latest antiparasitic drug was developed 40 years ago.
Research must be done in order to find antiparasitic candidates for development. Sea
cucumber has been shown to be a source of bioactive molecules such as antifungal,
cytotoxic, anti-arteriosclerotic, antioxidant and other properties. We embarked in a
bioassay guide study of sea cucumber presented in the Yucatan Peninsula as a source of
antiprotozoal agents. Four different sea cucumber; Holothuria grisea, H. floridana,
Astichopus multifidus, and Isostichopus badionotunus were collected and identified by
macroscopic features and by examination of the skeletal ossicles of their body wall.
Twenty adult organisms of each sea cucumber were eviscerated in order to remove the
Cuvier tubules, chopped, lyophilized and extracted with methanol. Crude extract were
separated by liquid-liquid extraction, followed by normal phase vacuum liquid
chromatography, then SPE using C18 cartridge, and finally with reverse phase LC-MS
(dereplication studies). All the fractions were evaluated in Artemia salina lethality test,
and antiprotozoal subcultered bioassay over G. intestinalis and T. vaginalis. Results
showed that crude extract were active except from I. badionotunus. Chromatography
separations reveals that polar fractions contains the maximum activity. IC50 over G.
intestinalis were 39.5 and 8.9 mg/mL for H. floridana, and A. multifidus respectively.
LCMS dereplication identified that bioactive molecules were triterpene glycosides.
References
3.
4.
5.
6.
7.
8.
9.
10.
11.
De-Xin, K; Ying-Ying, J; Hong-Yu, Z. Drug discovery today, 2010; pp 884-886.
Kelly, M.S. Echinodermata. Progress in Molecular and Subcellular Biology; Scotland, 2005; pp
139-165.
Solis-Marin, F.A; Arriaga-Ochoa, J.A; Laguarda-Figueras, A; Frontana-Uribe, S.C; DuránGonzález, A.
Holothuroideos (Echinodermata: Holothuroidea) del Golfo de México, México, 2009; pp 24-28.
Houssen, W.E; Jaspars, M. Methods in biotechnology, Natural products isolation, Totowa, New
Jersey, 2006; pp 353-390.
Raymond, G; Reid, D. S; Satyahit, D. S. Methods in biotechnology, Natural products isolation,
Totowa, New Jersey, 2006; pp 117-157.
Rahman, A; Choudhary, I; Thomsen, W. Bioassay techniques for drug development. San Diego,
USA, 2005; pp 8-10.
EPA Probit Analysis, Version 1.5. http://www.epa.gov/nerleerd/stat2.htm
Cedillo-Rivera, R; Muñoz, O. J. Med. Microbiol, 1992; pp 221-224.
Torres, M; Aguilar, M.B; Falcon, A; Sanchéz, L; Radwan, F.F.Y; Burnett, J.W; Hermier de la
Cotera, E.P; Arellano, R.O; , Toxicon, 2001, 1297-1307.
Hendler, G; Miller, J. E; Pawson, D. L; Kier, P. M. Sea strars, sea urchins and allies.
Echinoderms of Florida and the Caribbean. Washington, 1995; pp 285,286.
Posters Session 2
1.
2.
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Posters Session 2
UNPRECEDENTED 17-RESIDUE PEPTAIBIOTICS PRODUCED BY MARINEDERIVED Trichoderma atroviride
Catherine Roullier, Anne-Isaline Van Bohemen, Angélique Carroux, Aurore ZaloukVergnoux, Yves François Pouchus, Nicolas Ruiz
University of Nantes, Faculty of Pharmacy, 9, Rue Bias, 44035, Nantes, France.
Posters Session 2
In the course of investigations on marine-derived toxigenic fungi, five strains of
Trichoderma atroviride were studied for their production of peptaibiotics. While the
five strains were found to produce classical 19 -residue peptaibols, three of them
exhibited unusual peptidic sodium-adduct [M+2Na]2+ ions at m/z between 824 and 854.
These peptaibiotics, obtained as microheterogeneous mixtures after a chromatographic
fractionation, were identified by consecutive mass spectrometry fragmentations in ESIMSn. Twenty-nine sequences were identified, belonging to two series of unprecedented
17-residue peptaibiotics based on the model Ac-XXX-Ala-Ala-XXX-XXX-Gln-Aib-AibAib-Ala/Ser-Lxx-Aib-Pro-XXX-Aib-Lxx-[C129]. All sequences were characterized by a
constant peculiar residue in C-terminal position, displaying a mass of 129 Da. Elemental
formula C5H9N2O2 of the [C129] residue was established by HRMS and could
correspond to the cyclized form of Nd-hydroxyornithine, which has already been
observed at the C-terminus of various peptidic siderophores. Further studies are
conducted in order to confirm the structure hypothesis of the [C129] residue. Comparison
of the sequences for 17- and 19-residue peptides showed similarities for amino acids in
positions 1 to 16, suggesting a common biosynthesis pathway. Both new 17-residue
peptaibiotics and 19-residue peptaibols exhibited in vitro cytotoxicity against KB cells.
216
Posters Session 2
P 152
TOWARD THE TARGETED ISOLATION OF MARINE HALOGENATED
COMPOUNDS USING THE MEHALOCOA METABOLOMIC TOOL
Catherine Roullier, Yann Guitton, Elodie Blanchet, Marieke Vansteelandt, Marie
Geiger, Yves-François Pouchus, Olivier Grovel
University of Nantes, Faculty of Pharmacy, 9, Rue Bias, 44035, Nantes, France.
Numerous halogenated natural compounds have been described from all natural
sources. They are considered as biologically important and could play an interesting
role as lead compounds for drug discovery [1]. Despite the abundance of chlorine in the
marine environment, only nine compounds from marine -derived Penicillium strains
have been described to possess a chlorine atom in their chemical structure [2] and they
all displayed biological activities such as cytotoxicity for ligerin, a chlorinated
sesquiterpene which exhibited a specific antiproliferative activity against osteosarcoma
cell lines and in vivo antitumor activity [3]. In the course of our ongoing research on
bioactive fungal metabolites, investigating marine -derived Penicillium strains by LCHRMS/MS for new halogenated compounds appeared to be of great interest. In order to
simplify the data treatment and to fasten discoveries of natural halogenated compounds,
several addons for R XCMS were developed, such as the MeHaloCoA (Marine
Halogenated Compounds Analysis) metabolomic tool. All those R scripts were then
validated on chlorinated-compounds containing samples, which were analyzed on an
LC-ESI-IT-ToF apparatus (Shimadzu). Combining those scripts to a dereplication
approach allowed the rapid identification of new halogenated compounds from marinederived Penicillium genus and to consider their targeted isolation.
References
Gribble, G. W., Acc. Chem. Res. 1998, 31, 141-152.
The Dictionary of Natural Products online 21.2, 2013, CRC Press.
Vansteelandt M., et al., J. Nat. Prod. 2013, 76, 297-301.
Posters Session 2
1.
2.
3.
217
P 153
Posters Session 2
ELECTROSPUN MICRO/NANOFIBERS FROM MARINE
POLYSACCHARIDES FOR BIOMEDICAL APPLICATIONS
Stefanos Kikionis1, George Toskas2, Efstathia Ioannou1, Vassilios Roussis1
1
University of Athens, School of Pharmacy, Department of Pharmacognosy and Chemistry of Natural
Products, Panepistimiopolis Zografou, Athens 15771, Greece. 2Technological Educational Institute of
Piraeus, Department of Textile Engineering, 250 Thivon and Petrou Ralli Ave, Egaleo 12244, Greece.
Posters Session 2
Electrospinning is a relatively simple and versatile technique for the generation of
micro/nanofibers from polymeric solutions under application of high voltage electric
field. Significant progress has been made in the past few years and the applications of
electrospinning have spread in many fields, including the pharmaceutical sector.
Electrospun micro/nanofibers are promising materials for biomedical applications, such
as drug delivery, wound dressings and tissue engineering scaffolds. The increasing
variety of natural and synthetic polymers that can be electrospun provide researchers
with a broad spectrum of tools for tailoring the mechanical and biological properties of
fibers.
Natural polymers are frequently selected as materials with innovative and advanced
properties in the biomedical field due to their biocompatibility and biodegradability.
The wide spectrum of bioactivities exhibited by marine polysaccharides renders them
ideal biomaterials for the development of novel systems for tissue engineering and drug
delivery applications.
In the context of our continuous investigations towards the exploitation of bioactive
marine metabolites we turned our attention to polysaccharides from algae. A number of
marine polysaccharides including ulvans, alginates, agarose, and carrageenans from
various algal species were extracted, purified and electrospun in fibers. Experimenting
with blends of marine polysaccharides and other biodegradable polymers, such as
chitosan, PEO, PCL, PVA and cellulose acetate at different ratios and solvent systems
under a variety of experimental conditions (applied voltage, polymer flow rate, distance
to collector, etc.) allowed for the successful production of micro and nanofibers of
variable sizes and morphologies as evidenced by SEM analyses.
218
Posters Session 2
P 154
METABOLIC PROFILING OF Laurencia EXTRACTS FOR THE RAPID
DEREPLICATION AND DISCOVERY OF NEW NATURAL PRODUCTS
Katerina Kokkotou1,2, Marianna Nomikou1, Florian Pitterl2, Ariadni Vonaparti2,
Eleni Siapi2, Maria Zervou2, Efstathia Ioannou1, Vassilios Roussis1
1
University of Athens, School of Pharmacy, Department of Pharmacognosy and Chemistry of Natural
Products, Panepistimiopolis Zografou, Athens 15771, Greece. 2National Hellenic Research Foundation,
Institute of Biology, Medicinal Chemistry and Biotechnology, Division of Organic and Medicinal
Chemistry, 48 Vassileos Constantinou Ave., Athens 11635, Greece.
The cosmopolitan genus Laurencia represents an endless source of secondary
metabolites exhibiting a wide range of biological activities and thus it has been the
subject of intense research during the last decades. As a consequence, the need to
develop a fast and reliable screening tool to detect new secondary metabolites among
the pool of already isolated metabolites has emerged.
In this context, the metabolic profiling of Laurencia extracts was addressed by the
application of high throughput analytical techniques, namely LC-Orbitrap-MS and 2D
HSQC NMR spectroscopy. An integrated platform including sophisticated software
tools and databases, such as Xcalibur, ToxID, MarinLit and ACD/Labs, was developed
to mine the complex analytical data for the identification of known metabolites and
trace the presence of new natural products. In addition, an ‘in house’ database
incorporating NMR data from the relevant literature, as well as an LC-MS library of
algal metabolites isolated in our laboratory have been implemented.
Application of this screening approach to an extract of Laurencia specimen collected in
Kefalonia island led to the identification of ten previously reported metabolites and the
detection of two new natural products. Subsequently, phytochemical analysis confirmed
these results and led to the isolation and structure elucidation of two new bromoallene
acetogenins.
These results point out the potential of the direct screening of crude algal extracts in
order to detect new compounds, trace biomarkers and /or monitor the presence of
known bioactive metabolites.
Acknowledgements
Posters Session 2
This work is supported by the project “SysTerp”, which is implemented under the "COOPERATION
2009" Action of the "OPERATIONAL PROGRAMME COMPETITIVENESS AND
ENTREPRENEURSHIP" and is co-funded by the European Social Fund (ESF) and National Resources.
219
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Posters Session 2
FULL TRANSCRIPTOME ANALYSIS OF THE RED ALGA Laurencia
microcladia AND PRELIMINARY CHARACTERIZATION OF ITS TERPENE
BIOSYNTHETIC PATHWAYS
Fotini A. Trikka,1 Konstantinos Pasentsis1, Efstathia Ioannou2, Vassilios Roussis2,
Sotirios C. Kampranis3, Antonios M. Makris1, Anagnostis Argiriou1
1
Centre for Research and Technology Hellas, Institute of Applied Biosciences, Thermi, Thessaloniki
57001, Greece. 2University of Athens, School of Pharmacy, Department of Pharmacognosy and
Chemistry of Natural Products, Panepistimiopolis Zografou, Athens 15771, Greece. 3University of Crete,
Medical School, Department of Biochemistry, P.O. Box 2208, Heraklion 71003, Greece
Red algae exhibit important host-microbe interactions and can be considered as
ecosystems that co-evolve with their seaweed-associated microbial communities.
Nonetheless, molecular data describing the microbial species present and their
interactions are still limited. Laurencia is a genus of red algae that occurs worldwide
and is recognized as an important source of bioactive secondary metabolites, mainly
halogenated sesquiterpenes, diterpenes, triterpenes and C15 acetogenins.
In order to characterize these complex interactions and the produced terpenes, total
RNA was prepared from L. microcladia specimens and sequenced by Illumina
sequencing. 309,845 EST contigs of 167 bases mean length were assembled and used
for the construction of 40,746 Unigenes of 473 bases mean length. For the identification
of the associated microorganisms, BLAST searches against the 16S and nr databases
were performed. Results indicated a high number of sequences presenting similarity
with bacterial and unicellular organisms.
Posters Session 2
To illuminate the terpene biosynthetic pathways of red algae, with an emphasis to the
haloperoxidases, the resulted contigs were searched for halo- specific protein patterns.
One 283 bp contig with similarity to haloperoxidase genes was identified. Based on this
information, specific primers were designed and used in 3’-RACE experiments.
Sequence analysis of the isolated fragments identified four clones of 724 bp with
similarity to PAP2 haloperoxidase-like subfamily sequences. Further experiments
aiming to isolate the full length gene are underway.
Acknowledgements
This work is supported by the project “SysTerp”, which is implemented under the
"COOPERATION 2009" Action of the Operational Programme “COMPETITIVENESS
AND ENTREPRENEURSHIP” and is co-funded by the European Social Fund (ESF)
and National Resources.
220
Posters Session 2
P 156
INVESTIGATING SECONDARY METABOLITE BIOSYNTHESIS IN
MURICIDS: A MASS SPECTROMETRY IMAGING APPROACH
David Rudd , Maurizio Ronci, Taryn Guinan, Nicolas Voelcker and Kirsten
Benkendorff School of Biological Sciences, Flinders University of South Australia, Bedford Park, SA 5042.
Australia. Mawson Institute, University of South Australia, Mawson Lakes, SA 5095. Australia. Marine
Ecology Research Centre, Southern Cross University, Lismore, NSW 2480. Australia
In the last two decades molluscs have yielded a number of unique marine natural
products, generally in the form of secondary metabolites. Bioactive metabolites, by
nature, play specific functional roles in mollusc behaviour and their synthesis can be
quite temporal and behaviour driven. In order to better understand the origin and
biosynthetic activity of bioactive brominated indoles and choline esters from Australian
muricid, Dicathais orbita, we employed surface assisted mass spectrometry imaging.
Desorption / ionization on porous silicon (DIOS) and nano-assisted laser desorption /
ionization (NALDI) provided alternative functionalized scaffolds to spatially analyze
the two classes of low molecular weight compounds, without suppression of interfering
matrix signals. DIOS and NALDI imaging were able to successfully capture the in situ
distribution of metabolites from frozen fresh tissue sections. DIOS is also being applied
to investigate the temporal patterns of metabolite biosynthesis, in particular, sex specific
differences and maternally derived compounds associated with larval development.
Locating the site of metabolite biosynthesis has contributed to our understanding of
their ecological relevance and hopefully will contribute to their development as
potential medicinal compounds.
Posters Session 2
Figure 1. D. orbita hypobranchial gland cryo-section for: (A) Histology, (B) scanned on mass imaging
scaffold and (C) mass distribution maps of imaged tissue
221
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Posters Session 2
ACULAINES: NOVEL PEPTIDE TOXINS MODIFIED WITH LONG CHAIN
POLYAMINE FROM THE OKINAWAN MARINE SPONGE
Ryuichi Sakai, Satoko Matusnaga, Reimi Kishi
1
Hokkaido University, 3-1-1 Minato-Cho, 041 8611, Hakodate, Japan.
We have recently reported isolation and biological activity of peptide Aculaines (ACUs)
from the Okinawan sponge Axynissa acureata.1 ACUs are novel ribosomal polypeptide
containing long chain polyamine (LCPA) in the molecule. Three ACUs A-C, were
identified thus far. The molecular mass of those compounds 6600, 5700, and 2700 were
deduced from SDS-PAGE. Further analysis by MALDI-TOFMS data indicated that
ACU-A and-B are reasonably homogeneous but ACU-C present as complicated
mixture. Analyses of amino acid sequence of ACU-A and B indicated both share the 45amino acid peptide whose N-terminal residue was indicated, from the nucleotide
sequence of the gene encoding ACUs, to be tryptophan. In the Edman degradation,
however, the N-terminal amino acid was not detected but the sequencing started from
the second residue Tyr. Enzymatic hydrolysis of ACU-A and B afforded the N-terminal
tripeptides with the LCPA-containing N-terminal residue connected with Tyr-Asn.
Thus, the LCPA was shown to be attached to the N-terminal of the peptide. Further
structure determination was hampered because of difficulty in analyzing the NMR
spectrum for ACUs due to spectral complexity. We recently isolated, however, a new
LCPA-modified tryptophan (pACU-B) form the extract. The structure of pACU-B
strikingly implicated the structure of N-terminal residue for ACU-B allowing us to
propose a tentative structure of ACU-B. ACUs are found to show potent hemolytic
activity and disrupt cell membrane. Here we discuss recent progress in chemical and
biological investigation of the aculeines.
Posters Session 2
References
1.
222
Matsunaga et al. Chembiochem 2011, 12, (14), 2191-2200.
Posters Session 2
P 158
A NOVEL FAMILY OF QUINOPROTEINS WITH L-AMINO ACID OXIDASE
ACTIVITY
Antonio Sanchez-Amat, Jonatan C. Campillo-Brocal, María D. Chacón-Verdú,
Patricia Lucas-Elío.
Department of Genetics and Microbiology, University of Murcia, Murcia 30100, Spain
Marine bacteria constitute an enormous reservoir of biological diversity as revealed by
metagenomic studies. The marine gammaproteobacterium Marinomonas mediterranea
synthesizes LodA, a novel L-lysine- -oxidase. LodA is the first L-amino acid oxidase
described that does not oxidize the amino acid in the alpha position. An additional
difference is that LodA is not a flavoprotein, but contains a quinonic cofactor. LodA is
encoded by the lod operon containing the lodA gene plus a second gene, lodB, encoding
a protein required for LodA maturation.
Posters Session 2
Genome sequencing has revealed genes encoding proteins similar to LodA in different
bacteria. In some cases, lysine- -oxidase has been demonstrated. However, the actual
enzymatic activity of other proteins with different levels of similarity to LodA is
unknown. Genome sequencing of M. mediterranea revealed two genes, Marme_2396
and Marme_1655, similar to lodA. The characterization of a M. mediterranea mutant
strain with lod deletion indicated that it lacks lysine oxidase activity suggesting that
those genes must encode different enzymes. In this study, it is shown that Marme_1655
encodes a novel glycine oxidase that has been named GoxA. GoxA shows important
differences in terms of substrate range and sensitivity to inhibitors to other glycine
oxidases previously described. Similarly to lodA, goxA forms part of an operon with a
gene, goxB, homologous to lodB. These data indicate that proteins similar to M.
mediterranea LodA and GoxA may constitute a reservoir of novel L-amino acid
oxidases. These enzymes are of interest because of their biological activities and
biotechnological applications.
223
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Posters Session 2
ACTIVITY OF ISOLATED EXTRACTS FROM THE SEA ANEMONE
Bunodeopsis globulifera FROM THE MEXICAN CARIBBEAN
Judith Sanchez-Rodriguez, Juan Jose Dorantes-Aranda
Instituto de Ciencias del Mar y Limnologia-UNAM, , Unidad Academica de Sistemas Arrecifales, P.o.
Box 1152, Quintana Roo, 77500, Cancun, Mexico.
Posters Session 2
Sea anemones produce toxins that could be a source of drugs for medical use.
Bunedeopsis globulifera was collected, mashed to discharge nematocysts, frozen and
lyophilized. Crude extract was purified by liquid chromatography. Two fractions were
separated, and activity was assessed in ghost crabs Ocypode quadrata, and parasites
Giardia intestinalis and Trichomonas sp. Phospholipase activity was measured using
chicken egg yolk. Protein concentrations for crude extract, fraction 1 and 2 were 118,
223 and 30 μg mL-1, respectively. Protein sizes in crude extract ranged between 15 and
150 kDa fraction 1 from 15 to 250 kDa and fraction 2 from 25 to 100 kDa. Ghost crabs
did not exhibit lethal effects when injected with fractions 1 or 2 at 5 mg mL-1. However,
they did show lethal effects at 60 mg mL-1, including hemorrhage (crude extract and
fraction 1), shaking and paralysis (crude extract and fraction 2), with death occurring
within 6-11 min post-injection. Fraction 1 had the highest effect on parasites Giardia
intestinalis and Trichomonas sp., with 62 and 68.5% loss of viability, respectively, at
100 μg mL-1, and showed 11-43% loss of viability after exposure to crude extract and
fraction 2. Fractions 1 and 2 had similar phospholipase activity (Pz=0.19 at 48 hrs),
whereas crude extract phospholipase activity was almost two fold (Pz=0.35). Two
fractions were separated from the crude extract, showing phospholipase activity on egg
yolk, and lethal effects on ghost crabs and parasites. B. globulifera may be a source of
bioactive substances for potential use in pharmacology.
224
Posters Session 2
P 160
DIDEMNINS PRODUCTION BY TWO DIFFERENT STRAINS OF Tistrella
mobilis ISOLATED FROM A POLYCHAETE AND A SPONGE AT
PHARMAMAR
Carmen Schleissner, Pilar Rodríguez, Jesús García, Fernando de la Calle, Carmen
Cuevas
Microbiology R&D Dpt. PharmaMar SAL. Av. La Mina, 1, ES-28770, Colmenar Viejo (Madrid). Spain.
Didemnin B is a cytotoxic peptide isolated from the Caribbean tunicate Trididemnum
solidum by Rinehart in 1981. This compound showed significant in vivo antitumor
activity, but clinical trials were discontinued because of uncontrolled toxic effects.
Some years later, dehydrodidemnin B (Plitidepsin, Aplidin) was isolated from the
Mediterranean tunicate Aplidium albicans by PharmaMar researchers. Aplidin is being
developed by PharmaMar as a new oncology medicine and is currently in Phase III
clinical trials. The drug substance is manufactured by total chemical synthesis.
Surprisingly, two years ago at PharmaMar, bacterial didmenins B, nordidemnin B,
didemnin X and didemnin Y were all isolated from cultures of the á-proteobacteria
Tistrella mobilis. This bacteria was isolated from a sedentary polychaete collected in the
Indian Ocean. More recently, another T. mobilis didemnin producer has been isolated
from a sponge from the same geographic area. Simultaneously to our experimentation,
M. Tsukimoto published in 2011 bacterial production of didemnin B from T. mobilis
isolated from sediments collected in Japan1 and in 2012 Y. Xu also described didemnin
production from T. mobilis and T. bauzanensis in addition to a putative biosynthesis and
characterization of a hybrid NRPS/PKS gene cluster located in a plasmid.2
We have analyzed the kinetics of production, as a function of the fermentation
conditions and identified improved media.
The fact that these are free living bacteria and a knowledge of the didemnin gene cluster
opens the possibility of conducting gene modification to deflect the biosynthetic
pathway to produce plitidepsin.
References
Moriya Tsukimoto et al., J. Nat. Prod. 2011, 74, 1407-1411.
Ying Xu et al., J. Am. Che. Soc. 2012, 134, 8625-8632.
Posters Session 2
1.
2.
225
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Posters Session 2
VERTICAL SECONDARY METABOLITE GENE TRANSFER IMPLIES
SPECIES-SPECIFIC CYTOTOXIC COMPOUNDS IN ACTINOMYCETES
Carmen Schleissner, Pilar Rodríguez, Jesús García, Ana M Peñalver, Paz Zúñiga,
Xulio Benítez, Susana González, Fernando de la Calle, Carmen Cuevas
R&D Area, PharmaMar, S. A., Av. de los Reyes, 1, 28770 - Colmenar Viejo, Madrid, Spain.
Posters Session 2
A major problem for Natural Product Drug Discovery programmes is to avoid
rediscovering already known compounds, especially since developing and scaling-up
microorganism cultures, extraction, compound isolation and structure elucidation are all
very time and resource intensive activities.
During microbial antitumor drug discovery at PharmaMar, the analysis of more than
2600 active marine Actinomycetes by HPLC-mass spectrometry and dereplication
against our own database of cytotoxic compounds has identified a number of such cases
of redundancy.
Using an internal criteria based on identification of microbial species which all the
strains (more than 10) produce the same compounds, bioactive species have been
dropped directly for drug discovery without the need to cultivate. Such so-called
predictable species could be clear cases of the vertical transmission of genes.
Following this approach, currently 34 predictable species have been discarded as sure
producers of Actinomycins, antimycins, bafilomycins, staurosporine, echinomycin,
fluvirucins, geldanamycin, hygrolidins, piericidins, ikarugomycin, levorins and
rakicidins.
This approach allows us to select the strains most likely to produce novel compounds
and hence improve the efficiency and success of our Drug Discovery Process.
226
Posters Session 2
P 162
NATURAL INDUCERS FOR LARVAL METAMORPHOSIS IN
SCLERACTINIAN CORALS
Peter J. Schupp, Makoto Kitamura, Mareen Moeller, Masayuki Hatta
Institute of Chemistry and Biology of the Marine Environment. University Oldenburg. Germany
Posters Session 2
Many benthic marine invertebrates, including corals, disperse among the plankton
before settlement and metamorphosis. Finding a suitable habitat is especially important
for larvae of sessile marine invertebrates that upon settlement cannot respond to changes
in environmental conditions by moving to a more favorable environment. The ability of
larvae to detect habitat-specific cues has been recognized in a range of phyla, but until
recently, only a few studies identified the chemical structure of compounds involved in
larval settlement and metamorphosis. This study was aimed at identifying compounds
involved in the metamorphosis and settlement of scleractinian coral larvae. When
various chemical extracts of different crustose coralline algae (CCA) from Guam were
tested, only extract of Hydrolithion sp. resulted in high settlement rates. Bioguide
fractionation of the Hydrolithion extract (e.g. Hydrolithion itself and the associated
biofilms) revealed luminaolide to be a metamorphosis-enhancing macrodiolide, which
enhanced the larval metamorphosis of several coral larvae (Acropora surculosa,
Acropora globiceps, Leptastrea purpurea), indicating an unspecific metamorphosis
enhancer. Further experiments testing the involvement of CCA biofilms, as well as
biofilms from inert surfaces (e.g. tiles, bleached CCA), revealed that biofilms on
Hydrolithion and biofilms on certain inert surfaces more than three weeks old
repeatedly induced settlement in L. purpurea and Acropora larvae. Continued studies
lead also to the isolation of two settlement inducing bacteria (Pseudoalteromonas sp.),
from which 2 settlement and metamorphosis inducing compounds have been isolated.
Their structure elucidation is currently under way.
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Posters Session 2
STUDIES
S
TUDIES TOWARD
TOWARD THE
THE TOTAL
TO
OTAL S
SYNTHESIS
YNTHESIS O
OF
FP
PISCIBACTIN
ISCIBACTIN A
AND
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uri S
egade
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ar
a cos A. Montaos,
Moontaos, Katherine
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a Jaime
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Rodríguez,
ígguez, Carlos
Carlos
o
Yuri
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Departamento
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Química Fundamental,
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E-mail:
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The
Photobacterium
piscicida
T
he bacterium
bacterium P
hotobacterium dam
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selae ssubsp.
ubsp. pi
scicidaa iiss the
the aetiological
aetiological aagent
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n of
ffish
ish pasteurellosis
pasteurellosis also
also described
describeed as
as photobacteriosis
photobacteriosis (due to
to the
the change
chaannge in
in the
the
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axonom
mic ppos
ition)) or pseudotuberculosis,
ppseudotubberculosis, a disease
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g economic
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lossses
position)
iinn marine
marrine
n aaquaculture
quaculture w
orldwidee. From
From cultures
cultures of the
the aforementioned
afore
o mentioned bacteria,
bacteria, a new
n w
ne
worldwide.
ssiderophore
iderophhore named
named piscibactin
piscibactin (1)
(1) was
was isolated
isolated as
as its
its gallium
gallium and
annd iron(III)
iron(III) complexes
complexes
aalong
long with
with a possible
possible intermediate
intermediat
ate of its
its biosynthesis,
biosynthesis, prepiscibactin
preepiscibactin (2).
(2).1 S
Structure
tructuree of
resembles
pyochelin
ppiscibactin
iscibactin ((1),
1), which
which re
semblles tthe
he sstructures
tructures of ssiderophores,
iderophores, pyoc
helin aand
nnd
yersiniabactin,
ye
rsiniab
abactin,2 bears
bearrs one thiazolidine
thiazolidine ring,
ring, two
two thiazoline
thiazolinee rings
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annd a phenol,
phenol, and
and it
it is
is
ccharacterized
haara
r cterized by tthe
he pre
sence off five
five asymmetric
asymmetric centers.
centers.
presence
Posters Session 2
In tthis
his ccommunication
om
mmunication w
ill ffocus
oc
ocus on our re
sults on tthe
he ssynthesis
ynthesis of ccompounds
ompounds 1 and
annd
wee w
will
results
22.. W
r us
re
ing a convergent
convergent synthetic
synnthetic where
where the
the construction
construction of the
the thiazolidine
thiazolidine ring
ring
n is
is
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are
using
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the
h last
last steps
steps due to
to the
the instability
insstabbility of this
this heterocyclic
heterocyclic ring.
ring.
ng The
The use
use of LL- and
anndd DDccysteine
ysteinee aallowed
llowed us the
the stereoselective
stereoselective control
control of three
thre
h e stereocenters,
stereocenters, while
whilee a
Re
form
o at
atsky methodology
methodology permitted
permitted us the
the stereoselective
stereoselective
v control
control of the
the asymmetric
asymmetric
Reformatsky
ccenter
enter at
at C14. T
he pl
annned strategy
strategy should
should provide
provide a convenient
convenient access
access to
to the
the
The
planned
pre
paarat
r tion of pi
scibactin aanalogues
nnaloggues tthat
haat ccould
ould us
ed ffor
or
or cconjugation
onjugaation tthrough
hrough sspacer
paacer
preparation
piscibactin
used
aarms
rrms w
ith ffluorescent
luorescent probe
s.4
with
probes.
References
References
1.
Souto,
S u to , M
So
M.. A.
A. Montaos,
Montaos, A.
A. J.
J. Rivas,
R iv a s , M
Miguel
ig u e l B
Balado,
a la d o , C
C.. R
R.. Osorio,
Osorio, J.
J. R
Rodríguez,
o d ríg u e z , M
M.. L
L.. L
Lemos,
em o s, C
C..
J menez Eur.
Ji
Eur. J.
J. O
rg. Chem.
Chem. 2011,
20111, 55693.
693.
Jimenez
Org.
2. A.
A Ino,
Ino, A. Murabayashi,
Murabayashi, Te
trahedron 2001, 57,
57, 11897.
897.
Tetrahedron
3. M.
M Miethke,
Miethke, M. A.
A. Ma
rahiel, Mi
M
crobiol. Mol.
Mol. Biol.
Biol. Rev.
Rev. 2007,, 71
13.
Marahiel,
Microbiol.
71,, 4413.
4. S.
S Noël,
Noël, L.
L. G
uillon, II.. JJ.. Sc
halk, L;Gaëtan,
L;Gaëtan, A.
A. Mislin,
Mislin, Or
rg. Lett.,
Lett., 2010, 13, 8844.
44.
Guillon,
Schalk,
Org.
Acknowledgements
A
cknow
wledgements
This
Th
is w
work
ork is
is supported
supported bbyy G
Grant
rant AGL2012-39274-C02-02
AGL2012-39274-C02-02 (Ministerio
(Ministerio de E
Economia
conomia y Competitividad).
Competitividad)
d.
228
Posters Session 2
P 164
BIOACTIVE COMPOUNDS FROM A RED SEA CYANOBACTERIUM
Morea producens
Lamiaa Shaala1, Diaa Youssef2, Gamal Mohamed2, Zainy Banjar2, Sabrin Ibrahim3
1
King Abdulaziz University, King Fahd Medical Research Center, King Abdulaziz University, 21589,
Jeddah, Saudi Arabia. 2King Abdulaziz University, Faculty of Pharmacy, Jeddah, Saudi Arabia.
3
University of Taibah, Faculty of Pharmacy, Saudi Arabia.
Posters Session 2
Marine cyanobacteria are a prolific source of diverse classes of secondary metabolites.
Marine members of the genus Lyngbya (recently reclassified as Moorea) continue to
provide a structurally diverse array of compounds with different bioactivities including
peptides, macrolides and malyngamides. Bioassay-directed fractionation of a Red Sea
cyanobacterium Morea producens afforded two new compounds together with several
previously reported ones. The structures of the compounds were identified by extensive
1D and 2D NMR studies as well as high-resolution mass spectral determination.
Furthermore, different biological activities of the compounds will be presented.
229
P 165
Posters Session 2
BIOACTIVE SECONDARY METABOLITES FROM MARINE Bacillus spp
Hee Jae Shin, Fakir S. Tareq, Hyi-Seung Lee, Jong Seok Lee, Yeon-Ju Lee
Korea Institute of Ocean Science & Technology, 787 Haeanro, 426-744, Ansan, South Corea.
Posters Session 2
Marine Bacillus species produce versatile secondary metabolites including
macrolactones, polyketides, lipopeptides, polypeptides, and fatty acids. These
structurally diverse compounds exhibit a wide range of biological activities such as
antimicrobial, anticancer, antialgal, and others. In the course of our continuous study on
the bioactive secondary metabolites from marine microorganisms, we could isolate
novel antimicrobial and anticancer compounds from Bacillus spp. We present here the
isolation, structure determination and bioactivities of secondary metabolites from
marine Bacillus species.
230
Posters Session 2
P 166
FROM MARINE SPONGES INTO TISSUE ENGINEERING APPLICATIONS:
SPECIAL PROJECT APPROACH
Tiago H. Silva, Alexandre A. Barros, Ana L.p. Marques, Ana Rita C. Duarte, Joana
Moreira-Silva, Margarida B. Prata, Rui L. Reis
University of Minho -3b´S Research Group, Avepark, Zona Industrial da Gandra, S. Cláudio do Barco,
4806-909, Caldas das Taipas, Portugal.
Posters Session 2
Marine sponges are not only exceptionally rich in natural products, as also exhibit an
interesting extracellular matrix with fascinating morphologies and composition, being
mostly collagen and biosilica or calcium carbonate. Inspired by such features, SPECIAL
project has been established aiming at delivering breakthrough technologies for the
biotechnological production of cellular metabolites and extracellular biomaterials from
marine sponges. These include a platform technology to produce secondary metabolites
from a wide range of sponge species, which screening of biological activity is focus in
antitumoral bioactivity. Moreover, a novel in vitro method for the production of
biosilica is also pursued, as well as production of marine sponge collagen through
recombinant technology or extraction from maricultured biomass. These exciting
extracellular biomaterials motivate the development of porous structures to be used as
scaffolds for human tissue regeneration, following three complementary strategies.
First, collagen has been extracted from marine sponges and further processed as porous
structures by freeze-drying methodology. In parallel, marine sponges have been
extracted with water and ethanol and further treated with supercritical carbon dioxide to
remove salts and possible toxic compounds but also to decellularize the sponge tissues,
thus rendering a porous matrix composed of collagen. Regarding bioceramics, sponges
have been calcinated in order to obtain a silica-based porous structure, which exhibits a
bioactive behaviour. All the developed porous structures - scaffolds - can support the in
vitro culture and proliferation of cells aiming tissue regeneration.
231
Posters Session 2
232
Posters Session 2
P 167
Posters Session 2
P 168
DIFFERENCE IN THE PRODUCTION OF SECONDARY METABOLITES BY
Salinispora arenicola SUBJECTED TO DIFFERENT CULTURE CONDITIONS
Dulce Guillén-Matus1, Amayaly Becerril-Espinosa1, Ana Ma. Iñiguez-Martínez1,2,
Eliseo Almanza-Heredia1 and Irma E. Soria-Mercado1
1
2
Facultad de Ciencias Marinas, UABC. Km 103 Tijuana-Ensenada HW, 22830, Ensenada, BC. México;
Centro Universitario de la Costa, U de G. Av. Universidad de Guadalajara No. 203, Puerto Vallarta, Jal.
México.
Recent studies have revealed that genus Salinispora is a select group of marine
actinomycetes, considered the first forced marine genus and is characterized by
producing new secondary metabolites with unique chemical structures that possessing
antitumor, antiviral and immunosuppressive activities. In order to obtain information to
assist the development of new farming methods and technologies that allows access to
novel chemical compounds with biomedical application and additionally to understand
the complex adaptations that have this action bacteria genus in the environment, in this
research we analyzed the production of secondary metabolites from two bioactive
Salinispora arenicola strain (AMS300 and AMS22) isolated from sediments of the Gulf
of Californian México. Strains were subjected to 10 different culture conditions
enriched with oat and A1 media and variation of pH from 5.5, 6.7, 7.2, 8.5 and 11. The
compounds produced from the fifth to the tenth day, were monitored by molecular
weight using a liquid chromatography with mass detector. A correlation between
secondary metabolite production and variants considered was found. Differences in
secondary metabolite production between strains and an effect on the production of
these compounds caused by pH and culture media were found, indicating a complex
ecological adaptation for Salinispora arenicola. Most of the compounds obtained are
unknown, indicating that the strains of the AMS22 and AMS300 strains should be a
source of new biologically active compounds.
References:
2.
3.
Becerril-Espinosa A., Freel K.C., Jensen P.R., and Soria-Mercado I.E.2012. Marine
Actinobacteria from the Gulf of California: Diversity, Abundance and Secondary Metabolite
Biosynthetic Potential. Antonie van Leeuwenhoek 102(3).DOI 10.1007/s10482-012-9863-3.
Berdy J. 2005. Bioactive microbial metabolites .J. Antibiot. 58: 1-26.
Blunt J.W., Copp B.R., Hu W.P., Munro M.H.G., Northcote P.T., Prinsep M.R. 2008. Marine
Natural Products. Nat. Prod. Rep., 25(1): 35-94.
Posters Session 2
1.
233
P 169
Posters Session 2
SPIN-SPIN COUPLING CONSTANT APPROACH IN THE
STEREOCHEMICAL DETERMINATION OF FIVE-MEMBERED CYCLIC
ETHER ACETOGENINS FROM Laurencia marilzae
Adrián Gutierrez-Cepeda1,2, Antonio Hernández Daranas1,3, José J. Fernández1,2,
Manuel Norte1,2, and María L. Souto1,2
1
Instituto Universitario de Bio-Orgánica “Antonio González”, University of La Laguna, Av. Astrofísico
Francisco Sánchez 2, 38206 - La Laguna, Spain. 2Department of Organic Chemistry, University of La
Laguna, Av. Astrofísico Francisco Sánchez s/n, 38206 - La Laguna, Spain. 3Department of Chemical
Engineering and Pharmaceutical Technology, Faculty of Pharmacy, University of La Laguna, Av.
Astrofísico Francisco Sánchez s/n, 38206 - La Laguna, Spain.
The role of marine natural products in drug discovery passes through an accurate
structure determination. For that reason, the development of effective methods to solve
stereochemical problems has recently taken the limelight. In this context, new
techniques based in NMR spectroscopy and/or modern computational calculations are
paying off.
Recently, we presented a simple and efficient spin-spin coupling constant approach for
the challenging stereochemical analysis of five–membered rings.1 Here we report the
application to this method to achieve the relative assignment of five new C15
tetrahydrofuranyl-acetogenins isolated from the red alga Laurencia marilzae GilRodríguez, Sentíes et M. T. Funji,2,3 collected from Canary Islands.
Marilzafurollene A
Marilzafurollene D
Posters Session 2
References
1.
2.
3.
J. G. Napolitano, J. A. Gavín, C. García, M. Norte, J. J. Fernández, A. Hernández Daranas,
Chem. Eur. J. 2011, 17, 6338-6347.
M. C. Gil-Rodríguez, A. Sentíes, J. Díaz-Larrea, V. Cassano, M. T. Fujii, J. Phycol. 2009, 45,
264-271.
Gutiérrez-Cepeda, J. J. Fernández, M. Norte, M. L. Souto. Org. Lett. 2011, 13, 2690.
Acknowledges
This work was supported by grants SAF2011-28883-C03-01 and EU FP 7-KBBE-3-245137. A.G.-C.
MAEC-AECID for a Doctoral Fellowship. Authors thank Dr. M. C. Gil-Rodríguez (Departamento de
Biología Vegetal, University of La Laguna) for the taxonomic classification of the alga.
234
Posters Session 2
P 170
BEYOND N-METHYLATION: THE POTENTIAL OF ALKYLATION OF THE
BACKBONE OF CYCLIC PEPTIDES
Jan Spengler1, Ana I. Fernández-Llamazares1, Fernando Albericio2
2
1
IRB Barcelona, Baldiri Reixac 10, 08028, Barcelona, Spain.
University of Barcelona, Department of Organic Chemistry, Barcelona, 08028, Spain
Backbone N-methyl groups are found as constituents in many naturally occurring
bioactive peptides. Furthermore, the incorporation of N-methyl groups is an established
tool to improve pharmacological parameters of therapeutic peptides, and has also been
applied to enhance the activity and receptor selectivity of peptide ligands as a result of
conformational modulation.
We have investigated backbone amide groups as sites for structural modification. For
two model cyclic peptides, the effect of replacing N-methyl groups for other chemical
moieties was studied. On the example the peptide analog of Sansalvamide A, a
cyclodepsipeptide isolated from a marine organism [1], an N-triethylene glycol chain
(N-TEG) was incorporated at the different backbone positions with the aim of
modifying its physicochemical properties. On the example of Cilengitide [2], an RGDcyclopeptide developed as a highly active and selective V3-integrin ligand; its Nmethyl group was replaced for an N-(4-azidobutyl) group, which allowed for the
efficient conjugation of PEG through several chemical transformations. In both model
peptides, replacement of an N-Me by either the NTEG chain or the N-azidobutyl linker
provided a minimal impact on the original backbone conformation.
With these preliminary studies, we want to disclose the utility of the backbone amide
groups as sites for structural modification. As the synthesis of N-modified peptides
involved the acylation of N-alkyl residues, we want to discuss strategies to overcome
the inefficiency of such sterically demanding coupling steps.
References
2.
Belofsky, G. N.; Jensen, P. R.; Fenical, W.: Sansalvamide: a new cytotoxic cyclic depsipeptide
produced by a marine fungus of the genus Fusarium. Tetrahedron Lett. 1999, 40, 2913-2916.
Dechantsreiter, M. A.; Planker, E.; Mathä, B.; Lohof, E.; Hölzemann, G.; Jonczyk, A.; Goodman
S. L.; Kessler. H.: N-methylated cyclic RGD peptides as highly active and selective V3
integrin antagonists. J. Med. Chem. 1999, 42, 3033-3040.
Posters Session 2
1.
235
P 171
Posters Session 2
SEARCH FOR CYTOTOXIC MOLECULES FROM CORAL REEF TWILIGHT
ZONE
Junichi Tanaka, Wilmar Maarisit, Sona Rani Roy, Tsuyoshi Wauke, Idam
Hermawan, Mika Shingaki, Alisa Minei
1
University of the Ryukyus, Senbaru 1, Nishihara, 903-0213, Okinawa, Japan.
Coral reef twilight zone can be defined as the depth range from 40-50 m to 100 m or
so. As relatively fewer works have been reported on the metabolites of organisms in
this zone, we started to collect specimens of this area in 2005 and keep on working on
the material for unique bioactive molecules.1-3
An extract of the brilliant red bryozoa Calyptotheca sp. collected from Okinawa Is.
showed cytotoxicity against cultured cells. After isolation followed by spectroscopic
analysis and chemical modifications, we elucidated that the structures of active
principles are sodium salt of a steroid sulfate and its analogue.
We previously reported a series of spongian diterpenes from the sponge Dysidea cf.
arenaria collected from Okinawa Is.4 Another collection of the same species from
Irabu Is., 300 km west of Okinawa Is., furnished a different set of spongian
diterpenes suggesting geographic variation.
From a soft unidentified sponge collected from Iriomote Is., 450 km southwest of
Okinawa Is., we isolated a cytotoxic diterpene having an endoperoxide.
We will present isolation, structure elucidation, and bioassay results on the above new
and related compounds.
References
1.
2.
Posters Session 2
3.
4.
Tanaka, C.; Tanaka, J.; Bolland, R.F.; Marriott, G.; Higa, T. Tetrahedron 2006, 62, 3536-3542.
Tianero, M.D.B.; Hanif, N.; de Voogd, N.J.; van Soest, R.W.M.; Tanaka, J. Chem. & Biodivers.
2009, 6, 1374-1377.
Hermawan, I.; de Voogd, N.J.; Tanaka, J. Marine Drugs 2011, 9, 382-386.
Agena, M.; Tanaka, C.; Hanif, N.; Yasumoto-Hirose, M.; Tanaka, J. Tetrahedron 2009, 65, 14951499.
236
Posters Session 2
P 172
SEARCH FOR MOLECULES AGAINST HEPATITIS C VIRUS FROM CORAL
REEF ORGANISMS
Junichi Tanaka1, Furuta Atsushi2, Naohiro Noda3, Satoshi Tsuneda2, Hidenori
Tani3, Atsuya Yamashita4, Masamichi Nakakoshi5, Masayoshi Tsubuki5, Kazi Abdus
Salam6, Nobuyoshi Akimitsu6
1
University of the Ryukyus, Senbaru 1, Nishihara, 903-0213, Okinawa, Japan. 2Waseda University,
Tokyo, Japan. 3National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan.
4
Yamanashi University, Yamanashi, Japan. 5Hoshi University, Tokyo, Japan. 6The University of Tokyo,
Tokyo, Japan.
Hepatitis C is a chronic liver disease developing into fibrosis, cirrhosis, and
hepatocellular carcinoma. To treat the causative agent hepatitis C virus (HCV), a
combined medication with pegylated interferon-alpha and ribavirin is administered
often with newly introduced protease inhibitor telaprevir or boceprevir. However, due to
the side effects and ineffectiveness of the current therapy against several viral genotypes
in addition to enormous number of infected people in the world, there still is a demand
to supply new drug leads against HCV.
In our collaborative efforts to find antiviral molecules, we use two screening strategies:
enzyme assay against HCV NS3 helicase using photo-induced electron transfer (PET)
or FRET and replicon assay by replacing a part of the viral genome with a reporter
gene.
As results, we found a number of hit extracts from coral reef organisms with PET
assay and characterized the mode of action of manoalide,1 psammaplin A,2
cholesterol sulfate,3 and other phenol or sulfate molecules. On the other hand, we
detected chlorophyllone and another molecule with replicon assay.
We will present our screening results, identification of the molecules, and the mode of
action of the hit molecules.
References
Salam, K.A. et al. J. Nat. Prod. 2012, 75, 650-654.
Salam, K.A. et al. J. Nat. Med. in press.
Furuta, A. et al. J. Enz. Inhib. Med. Chem. in press.
Posters Session 2
1.
2.
3.
237
P 173
Posters Session 2
MICROCIONAMIDE
MI
ICROCIONAMIDE C,
C, A NEW
NEW CYTOTOXIC
CYTOTOXIC PEPTIDE
PEPTIDE FROM
FROM THE
THE
TANZANIAN SPONGE
SPONGE Clathria
Cllaatthria (T
C
Th
hallysiass) vvulpina
ulppina
TANZANIAN
(Thalysias)
Guillermo Tarazona,
Tar
a azona, P
Patrícia
aattrícia G
Gema
ema Cr
Cruz,
uzz,, Cr
Cristina
istina Cr
Crespo,
esp
spo,
p M
Marta
aarta Pérez,
Pérezz,, Al
Alejandro
lejandr
do
Guillermo
Martín,
Carlos
Eguilior,
Santiago
Bueno
and
M
ar
a tín, Car
loos de Egu
uiliorr, S
antiago Bu
eno an
nd Carmen
Carmen Cuevas
Cuevas
R&D
R&
DA
Area,
rea, PharmaMar
PharmaMar S.A.U.,
S.A.U., Pol.
Pol. Ind.
Ind. La Mina
Mina Norte,
N o r te , A
Avda.
vda. De los
los Reyes,
Reyes, 1,
1, 228770-Colmenar
8770-Colmenar Viejo
V ie jo
(Madrid), Spain.
S p a in .
(Madrid),
E-maail: gt
[email protected]
m
E-mail:
[email protected]
Posters Session 2
Microcionaamides A and
Microcionamides
and
n B are
arre marine
marrine peptides
peptides first
first isolated
isolated from
from
r
the
the Philippine
Philippine marine
mari
r ne
(Thalysias)
abietina.
ssponge
ponge Clathria
Clathria (T
Thal
h lysiass) abi
ietina.1 T
These
hese hexapeptides
hexaappeptide
d s are
arre characterized
charracterized by tthe
he
pre
sence of two
two cysteine
cysteine moieties
moieties that
thaat are
arre cyclized
cyclized through
througgh a cystine
cystine residue.
residue. No
No other
other
presence
aanalogues
nnaloguues of this
thhis ffamily
amily ha
avve be
en re
ported aand
nnd m
icrocionnamides A aand
nnd B ar
re tthe
he onl
oonlyy
have
been
reported
microcionamides
are
ttwo
wo pe
p ides iisolated
pt
solatted ffrom
rom
r
tthis
his ge
nus ssoo ffar.
ar. M
Microcionamides
icrocionnam
mides exhibit
exhibit considerable
consideraabble
peptides
genus
ccytotoxicity
ytotoxiicity aagainst
gainst different
different human
huumann breast
breast tumor
tumor cell llines
ines as well as antibiotic
anntibiiotic
aactivities.
ctivities.
marine
derived
In our ccontinuing
ontinuing eefforts
ffort
o s ttoo ssearch
earrcch ffor
or
o m
arine de
rived aantitumor
nntitumor ccompounds,
ompounds, a ssample
ampple
of the
thhe ssponge
p
ponge
Cl
athria (T
Thal
h lysiass)
s) vvulpina,
ullpi
p na, ccollected
ollected of
ff tthe
he ccoast
oast of M
twarra ((Tanzania)
Tannzani
n a)
Clathria
(Thalysias)
off
Mtwara
2010,, w
was
bioassay-guided
methanolic
iinn 2010
as sstudied.
tudied. By bi
oassayy guided ffractionation
rractionaation of iits
ts m
ethanolic eextracts,
xtracts, a ne
nnew
w
microcionamide
m
icrocionam
o mide ccongener
onge
g ner of this
this family
family named
nam
med microcionamide
microcionaamide C was
was isolated.
isolatted. The
The
new
ne
w molecule
mol
o ecule ccontains
ontains an
an isoleucine
isoleuccine residue
residue instead
instead of the
thee valine
valine moiety
moiety present
present in
in the
the
previously
pre
vioussly described
described microcionamides,
microcionaamides, and
annd retains
retains the
the transtrraanns- double
double bond in
in the
thee 2phenylethylenamine
residue,
in
phe
nylethylenaamine re
sidue, as
as found
found
o
in microcionamide
microcionam
mide A.
A.
The
T
he sstructure
truucture of microcionamide
microcionam
midee C was
was determined
determined by a combination
combinaation of 1D and
and 2D
N
NMR
MR experiments,
experiments, aass w
well
ell aass m
mass
ass sspectrometry.
pectrometry. T
The
he pure
p
ccompound
ompound w
was
as aassayed
ssayyed
aagainst
gainst di
ddifferent
fferent cancer
canncer cell
cell lines
lines and
annd showed
showed significant
significant
n cytotoxicity.
cytotoxicity.
References
R
eferences
1.
Rohan
R han A.
Ro
A. Davis
Davis et al.,
al., J. O
Org.
rg. Chem.,
C em., 2004, 69,
Ch
69, 44170-4176.
170-4176.
A
cknow
wkedgements
Acknowkedgements
•
•
•
238
Th
T
This
is w
work
ork was
was generously
generously supported
supported by
by a Torres
Torres Quevedo
Quevedo grant
grant from
from the
the Ministerio
Ministerio de
de
E
Ec
onomía y Competitividad,
Competitividad, Spain.
S p a in .
Economía
M
Mr
uysenaars (The
(The Pemba
Pemba channel
channel fishing
fishing club
club Shimoni).
Shimonni).
Mr.. P
P.. JJ.. R
Ruysenaars
M
Mi
nistry ooff L
ivestock aand
nd F
isheries D
evelopment. F
isheries D
epartment ((Republic
Republic of
of Tanzania).
Tanzania).
Ministry
Livestock
Fisheries
Development.
Fisheries
Department
Posters Session 2
P 174
SYNTHESIS OF CEMBRANOID ANALOGUES: A WAY TO IMPROVE THEIR
ANTIFOULING ACTIVITY
Edisson Tello,1,2 Leonardo Castellanos,1 Carmenza Duque,1,2
1
Departamento de Química, Universidad Nacional de Colombia, Bogotá, Colombia, AA 14490
2
Facultad de Ingeniería, Universidad de La Sabana, Bogotá
In previous studies, sixteen cembranoids isolated and identified from the octocorals
Pseudoplexaura flagellosa and Eunicea knighti,1,2 showed high antifouling activity
established by quorum sensing inhibition (QSI) test using Chromobacterium violaceum,
as well as bacterial biofilm inhibition against Pseudomonas aeruginosa, Vibrio harveyi
and Staphylococcus aureus.1,2 According to the results, the cembranoids were important
antifouling agents. In the present study we wanted to improve the activity shown by the
natural cembranoids via the preparation of synthetic analogues. Thus, we selected six
leads compounds,3 which showed antifouling activity, high concentration in the
octocorals source and reactive functional groups in their structures. The cembranoids
were then subjected to several fast, reproducible, and high yield regioselective reactions,
grouped as: epoxide ring opening, oxidations, treatment with iodine, photochemical
reactions, methylations and acetylations, and synthesis of cyclic hemiketals, to finally
obtain thirty four analogues.3 The stereostructures were established by extensive
spectroscopic analysis, by the NOESY experiments and by means of the modified
Mosher method.
The analogues obtained through the selected chemical transformations were tested
against the mentioned antifouling assays.3 Half of the analogues assayed showed
superior QSI and biofilm inhibition activity to the lead compounds, without interfering
in the bacterial growth; three cembranoids ((-)-(1R,2S,7R,3E,8E,11E)-18Acetoxycembra-3,8,11,15(17)-tetraen-2,7-diol,(-)-(1S,7R,3E,8E,11E)-18Acetoxycembra-3,8,11,15(17)-tetraen-7-ol,
and
(-)-(1R,2S,7R,3E,8E,11E)-2,18Diacetoxycembra-3,8,11,15(17)-tetraen-7-ol) displayed remarkable potency up to three
times higher than the natural compounds and was established that the presence of an
electronegative group in C-7 and an E-double bond in C-8,9 were responsible for the
activity. In conclusion, we have synthesized a pool of cembranoids that can be used as
antifouling agents.3,4
1.
2.
3.
4.
Posters Session 2
References
Tello, E.; Castellanos, L.; Arevalo-Ferro, C.; Rodríguez, J.; Jiménez, C.; Duque C. 2011.
Absolute stereochemistry of antifouling cembranoid epimers at C-8 from the Caribbean
octocoral Pseudoplexaura flagellosa. Revised structures of plexaurolones. Tetrahedron 67,
9112-9121.
Tello, E.; Castellanos, L.; Arevalo-Ferro, C.; Duque, C. 2012. Disruption in quorum sensing
systems and biofilm inhibition of bacteria by cembranoid diterpenes isolated from the octocoral
Eunicea knighti. J. Nat. Prod. 75, 1637-1642.
Tello, E.; Castellanos, L.; Duque, C. 2013. Synthesis of cembranoid analogues and evaluation of
their potential as quorum sensing inhibitors. Bioorg. & Med. Chem. 21, 242-256.
4 Duque, C.; Tello, E.; Castellanos, L.; Fernández, M.; Arévalo-Ferro, C. Bacterial Sensors in
Microfouling Assays. In State of the Art in Biosensors-Environmental and Medical Applications,
Rinken, T. Ed. Intech. Croacia, 2013, Chapter 4.
Acknowledgments. Colciencias and Universidad Nacional de Colombia support grants are greatly
acknowledged.
239
P 175
Posters Session 2
ORIGINAL HIGHLY HALOGENATED DERIVATIVES FROM
Asparagopsis taxiformis
Stephane Greff1, Mayalen Zubia2, Thierry Perez3, Olivier P. Thomas4
1
Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale IMBE UMR CNRS IRD
7263, Aix-Marseille Université, 3 place Victor Hugo, 13331 Marseille cedex 03, France. 2Agence pour la
Recherche et la Valorisation Marine, ARVAM, 2 rue Maxime Rivière, 97490 Sainte-Clotilde, La
Réunion. 3Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale IMBE UMR CNRS
IRD 7263, Station Marine d'Endoume, rue de la Batterie des Lions, 13007 Marseille, France. 4Institut de
Chimie de Nice UMR CNRS 7272, Université de Nice Sophia-Antipolis, Parc Valrose, 06108 Nice,
France.
Posters Session 2
Red algae are known to biosynthesize a wide range of halogenated metabolites.
Asparagopsis taxiformis (Rhodophyta, Bonnemaisoniaceae) has been shown to produce
numerous Halogenated Volatile Organic Compounds (HVOCs), with 1 to 4 carbons.
While this alga is suspected to expand worldwide, we implemented a research program
that aims at understanding the role of this secondary metabolome in marine
ecosystems.1 At first, chemical investigations were performed on A. taxiformis
gametophyte stages coming from the Indian Ocean. Unexpectedly, these studies
revealed two original and highly brominated cyclic metabolites 1 and 2. Structure
elucidations of 1 and 2 were achieved using spectroscopic methods including NMR and
GCMS. We will discuss biosynthetic hypotheses that might lead to these original 2,3dibromocyclopentenones. Then, as a first assessment of their role in the environment,
we assessed their biological activities using a standardized ecotoxicological assay.
References
1 http://seaprolif.ird.nc/
240
Posters Session 2
P 176
SESTERTERPENES
S
ESTERTER
T PENES FROM
FROM Ircinia
IIrrcin
nia sp.
s p.
Pere Fe
errioll1,11,2,2, Fr
Francisco
ancisco J.
J T
Toledo
oolledo1,1,2,2, Fr
Francisco
ancisco L
Leon
eon3, IIgnacio
gn
g acio Brouard
Brouard3, Ch
Christian
ristian
Pere
Ferriol
1
Tol
oledo
C. Toledo
1
Universidad
Un
iversidad de
de Las
Las Palmas
Palmas de
de Gran
Gran Canaria;
Canaria; 2In
Instituto
s titu to C
Canario
anario ddee Investigación
Investigación del
del Cáncer;
Cáncer; 3In
Instituto
stituto ddee
Productos Naturales
Naturales y Agrobiología.
A g ro b io lo g ía .
Productos
E-m
[email protected]
E-mail:
Posters Session 2
The
marine
Ircinia
Canary
Islands
rich
T
he m
arri
r ne ssponge
ponge Ir
cinia sspp ffrom
ro
rom Ca
annaarry Is
lands
n iiss a ri
ch ssource
ource of ssesterterpenes.
esterterpenes. In
tthis
his research
researrch we
we provide
provide recent
recent data
datta related
relatted w
ith this
this aspect.
aspect. The
The compounds
compounds where
whe
h re
with
iidentified
dentified as
as (8Z,13E,18R,20Z)-strobilinin
((8Z,,13E,,18R,20Z
,
))-strobilinin and
and
n (8E,13Z,18R,20Z)-strobilinin.
((8E,,13Z,,18R,20Z
,
)-strobilinin. The
The
1
m
ixture of strobilinins
strrobilinins has
has the
thhe appearance
apppe
p aran
r nce of oil
oil and
annd is
is homogeneous
hoomogeneous by TLC.
TLC. In 13
Cmixture
NMR
wee ccan
doubling
135.1),
N
MR spectroscopy
spe
p ctroscopy w
ann ssee
ee a dou
bling of signals
signals of the
the carbons
carrbons 8 ( 134.5/ 135
5.1),
123.5/
which
10 ( 12
23.5/ 124.5), 13 ( 134.9/ 135.7) aand
nnd 15 ( 123.9/ 125.1),
1
w
hich iinforms
nfform
o s us tthat
ha
h t
marine
natural
productt iiss a mixture
tthe
he m
arriine na
atural produc
mixture of the
the stereoisomers
stereoisomers
r (8Z,
(8Z, 13E)
13E) and
annd (8E,
(8E, 13Z),
13Z),
) in
in
with
described
aagreement
greement w
ith tthe
he de
scribed in
in bibliography
bibliograaphy
p 1,1,22. The
The sstructures
tructures w
were
ere cconfirmed
onffirmed by
H
RMS, and
and ttwo-dimensional
wo-dimensional nuc
clear m
agnetic re
sonaannce sspectroscopy
pectroscopy (CO
S Y, H
S QC
HRMS,
nuclear
magnetic
resonance
(COSY,
HSQC
aand
nnd H
MBC).
HMBC).
References:
References:
1
1.
2
2.
Rothberg
Rothberg I.,
I ., S
Shubiak
hubiak P.
P. (1975).
(1975). The
The structure
structure of
of ssome
ome antibiotics
antibiotics ffrom
rom the
the ssponge
ponge Ircinia
Irc in ia
strobilina. T
etrahedron Lett.,
Lett., 7769-772.
69-772.
strobilina.
Tetrahedron
Davis R.,
R., Capon
Capon R.J.
R.J. (1994).
(1994). Two
Two for
for one:
one: structure
structure revision
revision of
of the
the marine
marine sesterterpene
s e s te r te r p e n e
Davis
tetronic aacid
cid sstrobilinin
trobilinin too ((8Z,13E,20Z)-strobilinin
8Z,13E,20Z)-strobilinin aand
nd ((8E,13Z,20Z)-strobilinin.
8E,13Z,20Z)-strobilinin. A
ust
s . J.
tetronic
Aust.
Chem., 47,
47, 933-936.
933-936.
Chem.,
241
P 177
Posters Session 2
HETEROCYCLES
H
ETEROCYCLES
SA
AND
ND C
CERAMIDES
ER
RA
AMIDES F
FROM
ROM M
My
Myxilla
yxxilla ssp
p
P
ere Fe
F
rrioll1,11,2,2, Fr
Francisco
ancisco J.
J T
To
Toledo
oolledo1,1,2,2, Fr
Francisco
ancisco L
Leon
eon3, IIgnacio
gn
g acio Br
Brouard
ouard3, Rayco
Rayco
Pere
Ferriol
1
1
1
G
uedes , Jos
JoseJ.
eJ. S
Santana
antaana , Ch
Christian
ristian C.
C Toledo
Toolledo
Guedes
1
Universidad
Un
iversidad de
de Las
Las Palmas
Palmas de
de Gran
Gran Canaria;
Canaria; 2In
Instituto
s titu to C
Canario
anario ddee In
InvestigacióndelCáncer;
vestigacióndelCáncer; 3In
Instituto
stituto ddee
ProductosNaturales y Agrobiología.
ProductosNaturales
E-m
[email protected]
E-mail:
Posters Session 2
The
marine
Myxilla
Islands
Rich
T
he m
arrine ssponge
ponge My
yxilla sspp ffrom
ro
rom Canary
Cannarry Is
lannds iiss a Ri
ich ssource
ource of pyrimidines
pyrimidines aand
nnd
cceramides.
eraamide
d s. In this
this research
research we
we provide
provide recent
recent data
daata related
related with
with this
this aspect.
aspect. The
The
ccompounds
omppouunds where
where identified
identified as
as uracil
urracil (I),
( ), thymine
thym
y ine (II)
( ) and
and
n a ceramide
ceraamide mixture
mixture (III)
( ) or a
cceramide-1-phosphate
eraamide-1d
phosphaate mixture
mixture (IV).
(IV
V). The
The 1:1
1:1 mixture
mixture of pyrimidines
pyyrimidines has
has the
the aspect
aspect of a
w
hite ssolid
o id aand
ol
nnd iiss hom
ogeneous by T
LC. A
lthough iitt ha
en iisolated
solated ffrom
rom
r
ssponges
ponnges
white
homogeneous
TLC.
Although
hadd be
been
ffrom
rom
r
Inddonesia1, this
this is
is the
the first
first time
time described
described for
for
o the
the genus
genus
n Myxilla.
Myxilla. The
The ceramide-1ceraamidee-1Indonesia
phosphate
mixture
(IV)) ha
hass tthe
white
and
homogeneous
TLC
phosphaate m
ixture (IV
he aaspect
spect of a w
hite ssolid
olid an
nd aalso
lso iiss hom
ogeneous by T
LC
(Rf=
=0.60
0.600 in
in Cl3CH
CH// M
MeOH/
eOH/ AcOH/
AcOH/ H2O as
as eluent)
eluent) in
in agreement
agreement with
with the
the
bibliogrraapphy2.T
.The
he sstructures
tructures w
were
ere cconfirmed
onffirmed by H
HRMS,
R S, H
RM
HPLC-MS
PLC-MS and
annd ttwowobibliography
dimensional
nuclear
magnetic
resonance
(COSY,
NOESY,
HSQC
dimensional nuc
lear m
agnetic re
esonannce sspectroscopy
pectroscopy (C
COSY, N
OESY, H
SQC aand
nnd
HMBC)).
HMBC).
References
References
1
1.
2
2.
242
Karumanchi
Karumanchi V.
V.R.,
R., Bernard
Bernard D.S.,
D.S., Andrew
Andrew D.M.,
D.M., R
Raymond
aymond F.S.,
F.S., Babu
Babu L.T.,
L.T., Mark
Mark T.H.
T.H.
(2003). New
New manzamine
manzamine alkaloids
alkaloids with
with activity
activity aagainst
gainst iinfectious
nfectious aand
nd tropical
tropical parasitic
paraasitic
(2003).
diseases ffrom
rom an
an Indonesian
Indonesian sponge.
sponge. J.
J. N
a t. P
rod., 66, 823-828.
8233-828.
diseases
Nat.
Prod.,
Kratzer B.,
B ., S
chmidt R.R.
R.R. (1995).
(1995). Efficient
Effficient S
ynthesis ooff S
phingosine-1-phosphhate,
Kratzer
Schmidt
Synthesis
Sphingosine-1-phosphate,
Ceramide-1-phosphate, Lysosphingomyelin
Lys
y osphingomyelin and
and Sphingomyelin.
Sphingom
myelin. Liebigs
Liebigs Ann.,
Ann., 957-963.
957-963..
Ceramide-1-phosphate,
Posters Session 2
P 178
PRODUCTION
P
RODUCTION O
OF
FS
SPONGE
PONGE C
CYTOTOXIC
YTOTOXIC F
FACTORS
ACTO
ORS B
BY
YM
MARICULTURE
ARICULTURE
O Verongia
Veerongia aerophoba
V
aerophoba
OF
Peree Fe
rrioll1,11,22, Fr
Francisco
ancisco J. T
Toledo
oolledo1,1,22, M
Miquel
iquel Br
Brunet
unet1,11,22, María
Mar
a ía J. Mediavilla
Mediavilla1,
Ferriol
1,22
1,
1
Francisco
Francisco J.
J Estévez
Estévez , Ch
Christian
ristian C. Toledo
Toolledo
1
Universidad
Un
niversidad de
de Las
Las Palmas
Palmas de
de Gran
Grran Canaria,
Canaria, 2In
Instituto
s titu to C
Canario
anario ddee In
Investigación
vestigación del
del Cáncer.
Cáncer.
E-m
[email protected]
E-mail:
Posters Session 2
T
he m
arine ssponge
ponge Verongia
Verongia aerophoba
a rophoba from
ae
from
r
Canarry Is
lannds iiss a ri
ch ssource
ource of
The
marine
Canary
Islands
rich
bromotyrosine
brom
ottyros
y ine derived
derived cytotoxics.
cytotoxics.1 To
To obtain
obtain enough
enough of the
the bioactive
bioactive compounds
com
mpounds
p
for
foor
aapplication
ppplication iinn hum
ann ttherapy,
heraappy,
py ssponges
poonges have
havve to
to be cultured.
cultured.
d 2 Be
Before
fore
o sponge
sponge mariculture
marriculture
human
viable
method
must
iiss aaccepted
ccept
p ed aass a ccommercially
ommercially vi
able m
ethod of ssupplying
upplying bioactive
b oactive metabolites,
bi
metabolites, it
it m
ust
be de
monstrated tthat
haat aadequate
dequate produc
tion of sponge
sponge biomass
biomass and
annd metabolite
metabbolite is
is
demonstrated
production
pos
sible.3 In this
this study
study we
we provide
provide
d recent
recent data
daata related
relatted with
with both
both aspects.
aspects. Sponge
Sponge growth
groowth
possible.
rat
tes ha
avve bbeen
een measured
measured in
in terms
term
ms of projected
projected area,
arrea, and
annd the
the production
production of three
three main
main
rates
have
m
etabbollites (11R,17R
-eppi-Fistular
arin-3 II,, V
erongiolide III an
nd V
erongic Acid
Acid VI)) iinn
metabolites
(11R,17R-epi-Fistularin-3
Verongiolide
and
Verongic
diferent
have
been
measured
HPLC
(reverse
di
ferent cculture
ulture cconditions
onditions iinn ffish
ish ffarm
ar
arm eeffluents
ffluents ha
ave
v be
en m
easured by H
PLC (re
veerse
pha
se, M
eOH/ H2O as
as eluent).
eluent). T
These
hese re
results
sults sshow
how tthat
ha
h t tthe
h bi
he
bioprocess
oprocess iiss ffeasible.
easible. T
The
he
phase,
MeOH/
progresses
(Aeroplysinin
dienone
progresses towards
towarrds quantification
quaanntificattionn of cytotoxic
cytotoxic ffactors
actors (A
eroplysinin 1 III aand
nnd di
enone
n
V)
(dienone
V)) aalso
will
presented.
V) and
annd antileukemic
anntileukemic ccompound
ompound (d
dienone V
lso w
ill be pr
esented.
d
References:
R
eferences:
1.
2.
3.
Ferriol,
F rriol, P. Pr
Fe
Productos
oductos ccon
on actividad
actividad biológica
biológica ddee llaa eesponja
sp o n ja m
marina
arina Ve
Verongia
rongia aaerophoba
erophoba de
de las
la s
I la s C
Is
anarias. D
isertación ppara
ara llaa oobtención
btención del
del D
iploma de
de Estudios
Estudios Avanzados.
Avanzados. Universidad
Universsidad
Islas
Canarias.
Disertación
Diploma
d Las
Las Palmas
Palmas de Gran
Gran Canaria
Canaria (2008).
(2008).
de
M ller W.E.G.
Mü
W.E.G. et
et al.
al. Mar.
Mar. B
iothecnol. 1, 569
-579 (1999)
(1999)
Müller
Biothecnol.
569-579
D ckworth A.
Du
Battershill C.
C. Aquaculture,
Aqquaculture, 2221,
21, 3311-329
11-329 (2003)
(20033)
Duckworth
A.,, Battershill
243
P 179
Posters Session 2
MARINE
M
ARINE NATURAL
NATURAL PRODUCTS
PRODUCTS FROM
FROM SPONGES:
SPONGES: STEROLS
STEROLS INTO
INTO
My
M
yxxilla ssp.
p.
Myxilla
P
ere Fe
F
rrioll1,11,22, Fr
Francisco
ancisco J. T
Toledo
oolledo1,1,22,Fr
,Francisco
ancisco Leon
Leon3, IIgnacio
gn
g acio Brouard
Brouard3, Ch
Christian
ristian
Pere
Ferriol
1
C. Toledo
Toolledo
1
Universidad
Un
iversidad de Las
Las Palmas
Palmas de Gran
Gran Canaria.
Canaria. 2In
Instituto
s titu to C
Canario
anario ddee In
Investigación
vestigación ddel
el C
Cáncer.
áncer. 3In
Instituto
stituto ddee
Pr
oductos Naturales
Naturales y Agrobiología.
Productos
E-m
[email protected]
E-mail:
Posters Session 2
T
he m
arrine ssponge
ponge Myxilla
Myyxilla sp
sp from
from
r
Caana
n ry Islands
Islannds is
is a rich
riich ssource
ource of steroids.
steroids. In tthis
his
The
marine
Canary
sstudy
tudyy we
we provide
pprovide recent
recent data
datta related
relat
ated w
ith tthis
hhis aaspect.
sppect. The
The compounds
comppounds where
where identified
identified
with
aass sstigmast-5-en-3
tigm
mast-5-en-3 -ol
-ol ( -sitosterol)
-sitosterol) ((I,
I, 75%), stigmast-5,25-dien-3
stigmast-5,25t
dien-3 -ol
-ol (III,
(III, 7%),
7
stigmast-5,24(25)t
dien-3 -ol
-ol (V,
(V,, 2%) and
annd stigmast-5,23-dien-3
stigmast-5,23--dien-3 -ol
-ol (VII
(VII 16%). The
The
stigmast-5,24(25)-dien-3
mixture of stigmasterols
stigmasterols has
has the
the aspect
aspect of a white
white solid,
solid, is
is homogeneous
homogeneous by TLC
TLC and
and
mixture
25ºC
shows the
the physical
physical properties
properties as
as the
the main
main -sitosterol:
-sitosterol: m.p.
m.p. 277-278
277-278 ºC,
ºC, []
[]D25ºC
=shows
CHCl
15,2º (c 0,2; CH
Cl3).
244
Posters Session 2
P 180
CHEMICAL AND PHARMACOLOGICAL PROFILE OF EXTRACTS
OBTAINED FROM MARINE BACTERIA RECOVERED FROM SEDIMENTS
COLLECTED AT THE ST. PETER AND ST. PAUL ARCHIPELAGO, BRAZIL
Maria Torres1, Lourdes Ferreira2, Elthon Ferreira2, Karine Pires2, Paula Jimenez2,
Alison Silva1, Letícia Costa-Lutufo2, Otília Pessoa2, Edilberto Silveira2
1
Universidade Federal Do Ceara, Departamento de Química Orgânica e Inorgânica, 60510192, Fortaleza,
Brasil. 2Universidade Federal Do Ceará, Instituto De Ciências Do Mar, Fortaleza, Brasil.
Posters Session 2
The extension, localization and ecological aspects of the Brazilian coastal zone make it
a remarkable reservoir of compounds with pharmacological potential. This is
particularly interesting in the case of insular regions, such as oceanic islands and
archipelagos. Marine bacteria have shown to be an attractive source of structurally
diversified bioactive secondary metabolites. This study focused on the chemical
characterization and cytotoxic evaluation of the extracts produced from bacteria isolated
from sediment samples collected at the Saint Peter and Saint Paul Archipelago
(SPSPA), a group of 15 rocky islets located in the central equatorial Atlantic Ocean. A
preliminary investigation of ninety-three extracts obtained from marine bacteria strains
have been evaluated for their cytotoxic properties. Of those, twenty-three were
considered active, with IC50 values ranging from 0.04 to 20.5 μg/mL. The HR-LCMS
dereplication analysis combined with the AntiMarin database of the twenty-three active
extracts showed the occurrence of several know anticancer compounds, such as:
staurosporine derivatives, piericidin A, salinosporamycin A, obyanamide,
deoxytrichodermadiene, dechlororoseophilin, chaetongilin, ceratodictyo, toxin B,
penicidone B and, saliniketal A and B. It is worthy to point out that saliniketals A and
B, until now isolated only from Salinispora arenicola, was identified in fourteen strains,
being five of them S. arenicola. The other active extracts, to which no known
compounds were detected through the AntiMarin survey, are currently under chemical
investigation in order to find new active compounds.
References
1.
Williams PG, Asolkar RN, Kondratyuk T, Pezzuto JM, Jensen PR, Fenical W. J Nat Prod. 2007,
70, 83-8.
245
P 181
Posters Session 2
DECIPHERING AND UNDERSTANDING THE SECONDARY METABOLOME
OF THE MEDITERRANEAN SPONGE Haliclona sarai
Marie-Aude Tribalat1, Laura Gauro2, Jenny Rodriguez3, Adele Cutignano2, Angelo
Fontana2, Olivier P. Thomas1
1
Institut de Chimie de Nice, 28 Avenue Valrose, 06000, Nice, Francia. 2CNR Institute of Biomolecular
Biology, Via Campi Flegrei, 34, Pozzuoli (Napol), 80078, Italy. 3ESPOL Polytechnic University of the
Coast, Campus Gustavo Galindo Velasco, Km 30.5 Perimetral Road, Guayaquil, Eco 90112, Ecuador.
Marine sponges, as sessile filter feeders, produce a astonishing diversity of secondary
metabolites. Many of these compounds are potential new drugs against important
diseases like cancer but also bacterial, viral or parasitic infections. To better address the
supply issues of these important natural products more attention should be paid towards
the full description of their secondary metabolome but also to the corresponding
metabolic pathways.
The marine sponge Haliclona (Rhizoniera) sarai [1], belonging to the order
Haplosclerida, is only encountered in some Northwestern Mediterranean caves or deep
sea habitats. This sponge has attracted the interest of the chemists because the ability to
contain 3-alkylpydinium derivatives and the chemically-related alkaloids named
saraines. Several biological studies evidenced important pharmacological applications
of these compounds like antibacterial and antiviral potential [2-4].
In the frame of our ongoing investigation on sponge metabolites and secondary
metabolic pathways, we started investigating the full metabolome of this sponge in
order to identify possible precursors of the saraines. This preliminary chemical study led
to the isolation of new derivatives that may represent putative precursors of saraines.
Here we present the results of these studies together with the preliminary feeding
experiments with stable and radioactive labeled precursors of 3-alkylpyridines [5].
Posters Session 2
References
1.
2.
3.
4.
5.
246
http://www.marinespecies.org/porifera/porifera.php?p=taxdetails&id=244433
Cimino, G., C. A. Mattia, et al. (1989). "Unprecedented alkaloid skeleton from the
mediterranean sponge reniera sarai: X-ray structure of an acetate derivative of sarain-a."
Tetrahedron 45(12): 3863-3872.
Defant, A., I. Mancini, et al. (2011). "New Structural Insights into Saraines A, B, and C,
Macrocyclic Alkaloids from the Mediterranean Sponge Reniera (Haliclona) sarai." European
Journal of Organic Chemistry 2011(20-21): 3761-3767.
Lunder, M., G. Dreven ek, et al. (2012). "Cardiovascular effects induced by polymeric 3alkylpyridinium salts from the marine sponge Reniera sarai." Toxicon 60(6): 1041-1048.
Cutignano, A., A. Tramice et al. Biogenesis of 3-alkylpyridine alkaloids in the marine mollusc
Haminoea Orbignyana. Angew. Chem. Int. Ed 2003., 42: 2633-2636.
Posters Session 2
P 182
SEARCH
S
EARCH F
FOR
OR N
NEW
EW D
DRUG
RUG LEA
L
LEADS,
DS , W
WHICH
HICH C
CAN
AN ENHANCE
E
ENHANCE THE
THE EF
EFFECT
FEC
CT
O
FP
53, F
ROM M
A RI NE O
RGANISMS
OF
P53,
FROM
MARINE
ORGANISMS
Sachikko Tsukamoto,
Tsukamottoo,, H
Hikaru
ikar
k u Kato,
Kattoo, an
andd Tetsuro
Tetsuro Kawabat
Kawabata
ta
Sachiko
Kumamoto
Ku
mamoto University,
University, 5-1
5-1 Oe-honmachi,
Oe-honmachi, Ku
Kumamoto
mamoto 862-0973,
862-0973, Japan.
Japan.
E-maail: [email protected]
[email protected]
E-mail:
Posters Session 2
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Org. Lett.
Or
Lett. 2013, 15, 322.
2) Bioorg.
B oorg. Med.
Bi
Med. Chem.
Chem. Lett.
Lett. 2013,
2013, 23,
23, 33884.
884.
247
P 183
Posters Session 2
NEUROACTIVE
N
EU
UROACTIVE SMALL
SMALL MOLECULES
MOLECULES F
FROM
ROM TH
THE
HE W
WATER
ATER S
SOLUBLE
OLUBLE
E
EXTRACTS OF
OF PALAUAN
PALAUAN SPONGE
SPONGE A
ND TU
NICATE
EXTRACTS
AND
TUNICATE
Haajime U
chimasu1, An
Andrew
drrew Eng
Eng2, Geoffrey
Geoffrey S
Swanson
w
wan
nson2, Ryuichi
Ryuichi S
Sakai
akai1
Hajime
Uchimasu
2
1
Hokkaido
Ho
kkaido University,
University, 3-1-1
3-1-1 Minato-Cho,
Minato-Cho, 0041-8611,
41-8611, Hakodate,
Hakodate, Japan.
Japan.
Northwestern
No
rthwe
w stern University
University Feinberg
Feinberg School
Scchool of
of Medicine,
M e d ic in e , D
Department
epartment of
of Molecular
Molecular Pharmacology
Pharmacology and
and
Biological Ch
emistry, 303 E.
E. Chicago
Chicago Avenue,
Avenue, Chicago,
Chicago, 660611,
0611, US
A.
Biological
Chemistry,
USA.
E-m
[email protected]
E-mail:
Posters Session 2
Recently a grow
Recently
growing
ing number
number of neuroactive
neeuroactive molecules
molecules have
havvee been
been identified
identified from
frrom marine
mari
r ne
iinvertebrates.
nvertebra
b tes. In our continuing
continuing study
study to
to search
searc
r h for
for
o small
small molecules
molecules that
thatt modulate
moduulate
ssynaptic
ynaptic function,
func
u tion, we
we surveyed
surveyed marine
marine aqueous
aqueous extracts
extracts using
using mouse
mouse and
annd zebrafish
zebraafish
be
haavviors as
as principle
principle bioassays.
bioassays. Several
Several extracts
extracts were
were found
foouund to
to elicit
elicit striking
striking changes
channge
n s
behaviors
iinn behavior.
behaavvior. Two
Two of those
those extracts
extracts collected
collected in
in Palau
Palau were
weree subjected
subjected for
for
o separation.
sepaarraation. An
An
aaqueous
queouss marine
marine sponge
sponge extract
exttrract coded
coded Pal421
Pal421 induced
induced severe
seve
v re convulsions
convulsions in
in mice
mice (10
m
icro g/mouse,
g mouse, i.c.v.
g/
i.c.v. injection)
injection) but no significant
significant behavioral
behaavvioral changes
chaannges in
in zebrafish.
zebrafish.
micro
P
al421 aalso
lso ccaused
auused sspontaneous
pontanneouss eexcitatory
xcitatory burs
ts iinn vol
ltage-clamp re
cordings ffrom
rom
r
Pal421
bursts
voltage-clamp
recordings
ccultured
ultured ra
at hi
ppocam
mpal ne
urons. The
The extract
extract was
was separated
sepaarraated using
using Sephadex
Sephadex LH-20
LH-20 and
annd
rat
hippocampal
neurons.
tthe
he aactive
ctive
v ffraction
ra
r ction w
as puri
fied by
b H
PLC ttoo gi
ve know
ompound 11,, ((Z)-3,4,5,6,7,8Z))-3,4,5,6,7,8Z
was
purified
HPLC
give
knownn ccompound
hexahydro-1,3-diazocine-2,4-dicarboxylic
he
xaahhyddro-1,3-diazocine-2,4-dicarrboxylic acid,
acid, planar
planarr structure
struucture reported
reported in
in 1998 as
as a
new
ne
w lysine
lyssine derivative
derivaattive without
without biological
b ological activity
bi
activity1. Compound
Compound
p
1 iinduced
nduced cconvulsant
onvulsannt
be
haavviors in
in a dose-dependent
dose-dependent manner.
mannner. The
The absolute
abbsolute configuration
conffigura
g ation of 1 was
was determined
determined
behaviors
ttoo be 4S
4 by hydrol
ysis ffollowed
ol
o low
wed by M
arffey method.
methodd. A
nother eextract
xttrract ffrom
rom
r
aann
hydrolysis
Marfey
Another
uni
dentified tunicate,
tunicate, ccoded
oded P
al300, also
also elicits
elicits phenotypic
phenotyypic changes
changes in
in mice
mice and
and
unidentified
Pal300,
zzebrafish
ebrafish behaviors
behaviors and
annd modulated
modulated spontaneous
spontanneous synaptic
synaptic neurotransmission
n urotraannsmission in
ne
in cultured
culture
u d
ratt ne
uroons. Our
Our progress
progress in
in the
the isolation
isolation and
and identification
identificationn of the
thhe active
active molecules
molecules form
form
o
neurons.
P
al300 tunicate
tunicatte w
ill be discussed.
discussed. These
These studies,
studies, together
togethe
h r with
with the
the compounds
compounds we
we
Pal300
will
iidentified
dentified previously,
previously, underscore
underscore the
the rich
rich diversity
diversity of neuroactive
neurroactive molecules
molecules that
thaat await
await
di
scovery
r in
in marine
marrine orga
annisms.
discovery
organisms.
References
R
eferences
1.
248
Li,
L,C
Li
C.-J.
.-J. et
et al.
al. J. Nat.
N a t. P
Prod.
rod. 1998,
19998, 61 (3),
(3), 3387-389.
87-389.
Posters Session 2
P 184
BISTRATAMIDES
BI
STR
RATAMIDES K-N,
K-N, F
FOUR
OUR N
NEW
EW TH
THIAZOLE-CONTAINING
IAZOLE-CONTAINING C
CYCLIC
YCLIIC
H
EXAPEPTIDES F
ROM TH
EA
SCIDIAN Lissoclinum
Liissoclinum bistratum
biistrattum
HEXAPEPTIDES
FROM
THE
ASCIDIAN
Carlos
Urda
Car
los
o U
rda1, Elena
Ellena G
Gómez
ómez1, Fe
Fernando
rnando Reyes
Reeyes2, Al
Alfredo
lfr
f edo
d G
García-Cerezo
arcía-Cerezo1, Junichi
Junichi
3
1
1
Tanaka
Tan
a aka , Carlos
Carloos de Egu
Eguilior
uilior , S
Santiago
antiaago Bueno
Bueno and
and Carmen
Carmen Cuevas
Cuevas1
1
R&D Area,
R&D
A re a , P
PharmaMar
h a rm a M a r S
S.A.U.,
.A.U., P
P.. II.. L
Laa M
Mina
ina N
Norte,
orte, A
Avda
vda de
de los
los Reyes
Reyes 1,
1, 28770-Colmenar
V ie jo
(M
Madrid), Spain.
Spain. 2Fu
Fundación
ndación Medina,
Medina, Avda.
Avda. del
del Conocimiento
Conocimiento 3;
3; Edificio
Edificio C
Centro
entro de
de Desarrollo
D e s a rro llo
(Madrid),
Farmacéutico.
F rmacéutico. Parque
Fa
Parque Tecnológico
Tecnológico de
de Ciencias
Ciencias de
de la
la Salud.
Salud. 18016,
18016, Armilla,
Armilla, Granada,
Granada, Spain
Spain
3
Department
De
epartment of
of Chemistry,
Chemistry, Biology
Biology and
and Marine
Marine Science,
Science, University
University of
of the
the Ryukyus,
Ryukyus, Senbaru
Senbaru 1,
1,
Nishihara, Ok
inawa 903-0213,
903-0213, Japan.
Jap an .
Nishihara,
Okinawa
E-mail: cu
[email protected]
E-mail:
[email protected]
Posters Session 2
Ascidi
Ascidians
d anns of the
the genera
genera L
Lissoclinum
issocclinum aand
nd Didemnum
Didemnum are
arree prolific
prolific producers
producers of cyclic
cyc
y lic
peptides,
pe
ptide
d s, many
manny of which
which incorporate
inccorporaate modified
modified amino
amino
n acid
acid residues
residues containing
containi
n ng
tthiazole,oxazole,
hiazol
o e,oxazole, thiazoline,
thiazoline, or
o oxa
zoline ri
ngs, such
such as
as bistramides,
bistram
mides, bistratenes,
bistrattene
n s,
oxazoline
rings,
1,2)
ccomoramides
omorram
mides and
annd mayotamides.
mayotamides.((1,2)
In tthe
hhee ccourse
ourse of our screening
screeningg program
m to
to isolate
isolatte novel
noveel compounds
compounds with
with antitumor
anntitum
mor
prope
erties ffrom
rom
r
m
arrine ssources,
ources, w
ve iisolated
solated ffour
our
o r ne
w ccyclopeptides,
yclopeptides, na
amed
properties
marine
wee ha
have
new
named
bi
straatamides K
-N from
from
r
the ascidian
ascidiann L
issoclinum bi
stratum,
u of w
hich a re
presentat
ative
bistratamides
K-N
the
Lissoclinum
bistratum,
which
representative
bistratamide
eexample
xaampl
p e bi
strattam
mide K iiss sshown
how
wn bbelow.
elow.
T
hese ne
w compounds
compounds were
were obtained
obtained by column
colum
u n chromatography
chromatograapphy and
annd
These
new
ssemipreparative
emipre
p paara
rative H
PLC purification
purificattion of an organic
organic extract
extra
r ct of this
this organism.
orgaannism. Their
The
h ir
HPLC
were
determined
NMR)
sstructures
tructure
u sw
ere de
termined by NMR sspectroscopy
pectroscopy eexperiments
xpeeriments ((1D,
1D, 2D N
MR) aand
nnd
tthe
he aabsolute
b olute cconfiguration
bs
onffigurattion of the
the constituent
constituent amino
amino acids
acids was
was determined
determined in
in three
thre
h e
ssteps,
teps, involving
involving initial
initial ozonolysis,
ozonolysis, followed
fol
o lowed by acid-catalyzed
acid-catalyzed hydrolysis
hydrolysis and
annd
de
rivaattizattion w
ith M
arffey’s reagent.
reeagent. Bistratamides
Bistraatamides K-N
K-N
N were
were moderately
moderaately cytotoxic
cytotoxi
o c
derivatization
with
Marfey’s
aagainst
gainsst a pan
nel of tumor
tumorr cell
cell lines.
line
n s.
panel
R
eferences
References
1
1.
2.
Degnan,
Degnan, B.
B. M.;
M ; Hawkins,
M.
Hawkins, C.
C. J.;
J.; Lavin,
Lavin, M.
M F.;
F ; McCaffrey,
F.
McCaffrey, E.
E. J.;
J ; Parry,
J.
Parry, D.
D. L.;
L ; Watters,
L.
Watters, D.
D. J.
J J.
J
Med. Chem.
Chem. 1989, 32,
32, 11354-1359.
354-1359.
Med.
Rudi, A.;
A .; A
knin, M.;
M.; Gaydou,
Gaydou, E. M.;
M.; Kashman,
Kashman, Y.
Y. Tetrahedron.
Tetrahedron. 1998, 54,
54, 113203-13210.
3203-13210.
Rudi,
Aknin,
Acknowkedgements
Ac
knowkedgements
•
•
•
•
Sa
Sam
m Ratulangi
Ratulangi University
University ooff Manado.
Manado. Indonesia.
Indonesia.
Un
iversitá Politecnica
Politecnica De
lle Marche
Marche Ancona.
Ancona. Italy.
Italy.
Universitá
Delle
Mi
nistry ooff Ma
rin e A
ffairs aand
nd F
isheries (Republic
(Republic of
of Indonesia).
In d o n e s ia ).
Ministry
Marine
Affairs
Fisheries
Dr
v ie r T
urón ((CEAB-Centro
CEAB-Ceentro ddee E
s tu d io s A
vanzados de
de Blanes).
Blanes).
Dr.. Xa
Xavier
Turón
Estudios
Avanzados
249
P 185
Posters Session 2
ISOLATION OF THE OUTER-MEMBRANE IRON TRANSPORTER FRPA
FROM THE FISH PATHOGEN Photobacterium damselae subsp. piscicida FOR
STRUCTURAL STUDIES AIMED AT THE RATIONAL DESIGN OF NEW
GENERATION ANTIBACTERIALS
Katherine Valderrama1, Carlos Jiménez1, Miguel Balado2, Jaime Rodríguez1, Manuel
Lemos2, Anton Vila1
1
Universidad de La Coruña, Departamento de Química Fundamental, Facultade de Ciencia , Campus
Zapateira, S/N, 15071, A Coruña, Spain. 2University of Santiago de Compostela, Institute of Aquaculture,
Department of Microbiology and Parasitology, 15782, Santiago de Compostela, Spain.
Pasteurellosis, caused by the fish pathogen Photobacterium damselae subsp. piscicida,
is considered one of the bacterial fish diseases with greatest economic impact.1 Our
group has previously identified and characterized a subset of genes from P. damselae
subsp. piscicida involved in virulence for fish. Most of these genes encode proteins
involved in the synthesis of the siderophore piscibactin. In addition, these studies led to
the identification of protein FrpA as the piscibactin outer membrane receptor. Later
genetic comparative studies and chemical analysis performed by our group resulted in
the structural characterization of the complex piscibactin-Ga(III).2
In this communication, we want to present our advances pursuing the structural analysis
of the complex FrpA - piscibactin-Fe (III) by means of X-ray crystallography. To this
end, we have constructed an arabinose-inducible overexpression plasmid by overlapextension PCR cloning. This vector contains the predicted sequence of the mature FrpA
protein preceded by the pelB targeting peptide and a 10-His sequence. We expect that
the fusion protein can be correctly targeted to the outer membrane of E. coli cells from
where it can be easily purified by affinity chromatography. Obtaining a detailed picture
of the interaction between piscibactin-Fe(III) and its receptor protein FrpA, it will
provide the kind of knowledge necessary for the rational design of piscibactin
conjugates which can serve as new-generation antibacterials against pasteurellosis.
References
J. L. Romalde, Int. Microbiol. 2002, 5, 3. 2.-A. Souto, M. A. Montaos, A. J. Rivas, M. Balado,
C. R. Osorio, J. Rodríguez, M. L. Lemos, C. Jiménez, Eur. J. Org. Chem. 2012, 5693.
Posters Session 2
1.
250
P 186
251
Posters Session 2
Posters Session 2
P 187
Posters Session 2
METABOLOMICS AS A TOOL IN THE IDENTIFICATION AND
PRODUCTION OF NEW MARINE-DERIVED ANTIBIOTICS FROM
SPONGES AND ENDOSYMBIOTIC BACTERIA
Christina Viegelmann1, Cheung Hoe Leong1, Jennifer Parker1, Carol Clements1,
Usama Abdelmohsen2, Ute Hentschel2, Lekha Menon3, Jonathan Kennedy3, Alan
Dobson3, RuAngelie Edrada-Ebel1
1
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
2
Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Würzburg, Germany.
3
Environmental Research Institute, University College Cork, Cork, Ireland.
E-mail:[email protected]
Posters Session 2
Metabolomic methods can be utilised to screen diverse biological systems for
potentially novel and sustainable sources of antibiotics and pharmacologically-active
drugs. Marine sponges and their endosymbionts have proven to be abundant sources of
bioactive compounds. HR-LCFTMS and NMR were used in the identification of
compounds isolated from a bacteria and its host sponge, as well as in the dereplication
and metabolic profiling of other sponge-associated bacteria.
24-methylenecholesterol and two novel steroids, all significantly active against
Trypanosoma brucei, were isolated from the Irish Sea sponge Haliclona simulans.
Extracts from Streptomyces sp. isolated from H. simulans demonstrate anti-bacterial and
anti-fungal activities. HR-LCFTMS assisted in identifying antimycins as the anti-fungal
compounds. NMR and HR-LCFTMS were applied to the dereplication of extracts from
bacteria from Mediterranean sponges. EG4 was selected and its cultivation optimised
from small scale to larger scale production, under different media conditions, with the
aid of metabolomic methods and multivariate analysis to identify and trace biomarkers.
Metabolomics has become a powerful tool in systems biology which allows us to gain
insights into the potential of natural marine isolates for synthesis of significant
quantities of promising new agents, and allows us to manipulate the environment within
fermentation systems in a rational manner to select a desired metabolome.
252
Posters Session 2
P 188
EXPLORING THE NATURAL PRODUCTS OF AN ALIEN SEA CUCUMBER
IN THE MEDITERRANEAN SEA: Synaptula reciprocans
Gabriela Vinueza-Hidalgo1, Paraskevi Louizidou2, Rainer Ebel3, and Frithjof
C.Küpper4
1
School of Biological Sciences, University of Aberdeen, Scotland, UK. 2 Department of Zoology Marine Biology, School of Biology, University of Athens Panepistimiopolis, Athens, Greece. 3 Marine
Biodiscovery Centre, University of Aberdeen, Scotland, UK. 4 Oceanlab, University of Aberdeen,
Scotland, UK
The Mediterranean Sea is biologically diverse, but has undergone great change since the
opening of the Suez Canal in 1869 1. This has led to the establishment of over 925 Red
Sea species in the Mediterranean basin, also known as the Lessepsian invasion.2,3
Invasive species are considered the second most important cause of global diversity
change and thus a threat impacting local biodiversity and species richness. One such
Lessepsian invasive species is the Red Sea holothurian Synaptula reciprocans, which
was first recorded in 1926.4 It is a species with established success and dispersal that
apparently follows circulation patterns of Atlantic water masses.4,5 So far, it has been
described from the coasts of Cyprus, Israel, Lebanon, Syria, Turkey and Greece. Given
its large size and abundance in most of the areas it has colonized, it is likely to have a
significant effect on the ecosystem. Its successful dispersal and establishment may be
the result of a variety of defense or allelopathic mechanisms. To date, Synaptula
reciprocans appears not to have been chemically studied. Our preliminary analysis of its
crude methanolic extract by LC-MS did not provide any evidence for the presence of
steroid or triterpene glycosides that have been reported for the related Synapta
maculata.6,7 The results of our current attempts at isolating and characterizing the
metabolites of Synaptulareciprocans and tests for biological activity will be reported.
References
4.
5.
6.
7.
Zibrowius, H. Mésogée. 1991, 51, 83-107.
Fishelson, L. Italian Journal of Zoology. 2000,, 67, 393-415
Mollo, E., Gavagnin, M., Carbone, M., Castelluccio, F., Pozone, F., Roussis, V., Templado, J.,
Ghiselin, M.T., Cimino, G. PNAS. 2008, 105, 4582- 4586.
Mortensen, T. The Transactions of the Zoological Society of London. 1926, 22, 117-131.
Cherbonnier, G. Bulletin du Muséum national d'histoire naturelle. Section A, Zoologie, biologie
et écologie animales. 1986, 8, 43-46.
Kumar, SVASP., Dhananjaya, N., Reddy, GBS. Journal of Chemical Research. 1998, 7, 404405
Avilov, SA., Silchenko, AS., Antonov, AS., Kalinin, VI., Kalinovsky, AI., Smirnov, AV.,
Dmitrenok, PS., Evtushenko, EV., Fedorov, SN., Savina, AS., Shubina, LK., Stonik, VA.
Journal of Natural Products. 2008, 71, 525-531.
Posters Session 2
1.
2.
3.
253
P 189
Posters Session 2
STRUCTURE-ANTIMALARIAL
S
TRUCTURE-ANTIMALARIAL ACTIVITY
ACTIVITY RELATIONSHIP
RELATIONSHIP STUDIES
STUDIES OF
OF
THE
NEW
ZEALAND
MARINE
NATURAL
PRODUCTS
DIDEMNIDINE
TH
EN
EW ZEA
LAND M
AR INE N
ATURAL P
RODUCTS D
IDEMNIDINE B
AND
A
ND ORTHIDINE
ORTHIDINE F
1
Jiayi
Wang,
Ji
iaayi W
an
a gg,, M
Marcel
ar
a cel Kai
Kaiser,
iserr,,2,2,33 Br
Brent
ent R.
R Copp1
1
School
Sc
hool of
of Chemical
Chemical Sciences,
Sciences, University
University of
of Auckland,
Auckland, P
Private
rivate B
Bag
a 992019,
ag
2019, Au
Auckland
ckland 11142,
142, Ne
New
w
Ze
a l a n d . 2S
Swiss
wiss Tropical
Tropical and
and Public
Public Health
Health Institute,
Institute, Socinstrasse
Socinstrasse 557,
7, P
PO
O Box,
Box, CH-4002
CH-4002 Basel,
B a s e l,
Zealand.
Switzerland. 3Th
Thee University
University of
of Basel,
Basel, CH-4003
CH-4003 Basel,
Basel, Switzerland.
Switzerland.
Switzerland.
E-ma
ail: [email protected]
[email protected]
E-mail:
Parasitic
P
arrasitic protozoal
protozoal infection
inffection leading
leadiing to
to neglected
neglected tropical
tropical diseases
diseases is
is a cause
cauuse of suffering
suffferi
r ng
ffor
or
o an
an estimated
estimated one billion
billion people
peopple worldwide.1
worldwide.1 While
While drugs
drrugs exist
exist for
for
o these
these diseases,
diseases,
th
ey ha
avve unde
sirabble sside-effects
ide-effects or ar
re sshowing
howing re
duuced eefficacy
fficacy ffrom
rom
r
grow
wing
they
have
undesirable
are
reduced
growing
pre
valenc
n e of drug resistant
resistannt strains.
strains.1 Polyamines
Polyam
mines are
arre well
well recognized
recognized as
as a biologically
biologically
prevalence
active
active sscaffold
caffoold exhibiting
exhibiting anti-protozoal
annti-prootozoal activities.
activities.2 E
Evaluation
valuaation aagainst
gainst ne
neglected
glected di
disease
sease
parasite
natural
productt di
didemnidine
pa
arrasite ttargets
arrgets iindicated
ndicated tthe
he na
atural produc
demnnidine
n B ((1)
1) as
as a mildly
mildly active
active
ccompound
ompouund towards
towarrds the
the malaria
malarria parasite
parrasite P
lasmodium ffalciparum,
aalcipparum, how
ever with
with notable
notable
Plasmodium
however
ccytotoxicity.
ytotoxiicity.3 T
The
he ssame
ame prot
protozoal
ozzoal screening
screening programme
prograamme identified
identified the
the ascidian
ascidi
d an
m
etabol
b lite ort
hidine F ((2)
2) as
as being
beingg a non-toxic,
non-toxic, moderate
moderate growth
grrowth inhibitor
inhibitor off malaria.
malarria.4
metabolite
orthidine
Posters Session 2
With the
the
h aim
aim off discovering
discoveriing new
new classes
classes off antimalarial
ant
ntimalarriial agents,
agentts, we
we have
havve synthesised
ha
syntthhesised
With
novel
novel compounds
com
o pounds that
thaat contain
contain structural
struc
r tural features
features of both
both natural
n tural product
nat
product templates,
templattes, and
annd
evaluaated all
all ccompounds
ompounds against
against drug
d
resistannt strains
strains of P.
P. falciparum.
faalcipparum. Thus,
Thus, analogues
annalogue
g s
evaluated
resistant
bearing
beari
r ng variously
vaari
r ously substituted
substituted indole
inddole moieties
moieties with
with different
different polyamine
polyamine chain
chain lengths
lenggths
were
were synthesized
synt
y thhesized and
and characterised.
charracterised. The
The analogues
analogues were
were evaluated
evaluatted against
against P.
P.
falciparum
faalcipar
p rum in
in vitro,
vitro, which
which lead
lead to
to the
the identification
identification of
o an
an extremely
extremely potent
potent lead
lead
compound
compouund which
which was
was further
furt
u her subjected
subbjected to
to in
in vivo
vivo analysis.
annalysis. The
The results
results of SAR
SAR analysis
annalysis
annd both
both in
in vitro
vitro and
and in
in vivo
vivo evaluation
evalua
u tion will
will be presented.
presented.
and
R
eferences
References
1. Watts,
Watts, K
.; T
enney, K.;
K.; Crews,
Crews, P.
P. Curr.
C rr. Opin.
Cu
Opin. Biotechnol.
Biotechnol. 2010, 21,
21, 8808-818.
08-818.
K.. R
R.;
Tenney,
2. Bi,
B i, X
.; L
opez, C.;
C .; B
acchi, C.
C. J.;
J.; Rattendi,
Rattendi, D.;
D.; Wo
oster, P.
P. M.
M. Bioorg.
Bioorg. Med.
Med. Chem.
Chem. Lett.
Lett. 2006, 16
229X.;
Lopez,
Bacchi,
Wooster,
16,, 332293232.
3. F
inlaysson, R.;
R.; Pearce,
Pearce, A.
A. N.;
N.; Page,
Page, M.
M. J.;
J.; Kaiser,
K a is e r, M
.; B
ourguet-Kondracki, M.
M. L.;
L.; Harper,
Harper, J.
J. L.;
L.; Webb,
W ebb,
Finlayson,
M.;
Bourguet-Kondracki,
V. L
.; C
opp, B.
B. R.
R. J. N
a t. P
rod. 2011, 74,
744, 8888-892.
88-892.
L.;
Copp,
Nat.
Prod.
4. Liew,
Liew, L.
L. P.
P. P.;
P.; Kaiser,
Kaiser, M.;
M.; Copp,
Copp, B.
B. R.
R. Bioorg.
Bioorg. Med.
Med. Chem.
Chem. Lett.
Lett. 2013,
20113, 23,
23, 4452-454.
52-454.
254
Posters Session 2
P 190
TOWARDS
TO
WARDS THE
THE S
SYNTHESIS
YNTHESIS O
OF
FM
MARINE
A RI NE D
DITERPENOID
ITERPENOID C
CALYCULONE
ALYCULONE A
AND MARINE
MARINE HYDANTOIN
HYDANTOIN ALKALOID
ALKALOID P
ARAZOANTHINE A
AND
PARAZOANTHINE
Johannes Wefer,
Wefferr,, Kr
Kristina
istina Simon,
Simon, Thomas
Thom
mas Lindel
Lindel
Johannes
TU Braunschweig,
Braunschweig, Institute
Institute of
of Organic
Organic Chemistry,
C h e m is try , H
Hagenring
agenring 330,
0, 338106
8106 B
Braunschweig,
ra u n s c h w e ig , G
Germany
erm an y
[email protected]
E-mail:
[1]]
Calyculone
Calyculone
o A belongs
belongs to
to a group
group of rare
raarre diterpenoids,
diterpenoids, the
the cubitanoids
cubitannoids[1
ssharing
haarring
n a
twelve-m
membered monocyclic
monocyclic skeleton.
ske
k leton. This
This scaffold
scaffol
o d is
is named
naamed after
after (+)-cubitene
(+)-cubitene (1)
(1) a
twelve-membered
naatural product
produc
d t from
from
r m the
the
h termite
termite Cubitermes
C bitermes
Cubi
natural
[2]]
umbratus.[2
S
Several
everal related
r lated oxy
re
oxygenated
genatted cubitanecubitan
aneumbratus.
type diterpenoids
diterpenoids such
such as
as calyculone
calyculone A (2)
(2) have
h ve
ha
type
3]
been isolated
isolated from
frrom marine
marrine gorgonian
gorgonian corals.
corals.[[3]
2
been
shows
SR
shows strong
strong in
in vitro
vitro
r cytotoxicity
cytotoxicity aagainst
gainst S
R
leukemia,
melanoma
UACC-62,
leukemia, m
elannoma U
ACC-62, and
annd RXF
RXF 393 renal
reenal
[4]]
cancer
canc
n er ccell
ell llines.
ines.[4
Except
Exc
x ept ffrom
rom
r
1 no ccubitanoids
ubitanooids
have
been
ha
avve be
en ssynthesized
ynthesized ssoo ffar.
ar.
r
Re
cently w
veloped a nov
el route
route towards
towards the
the
Recently
wee de
developed
novel
ccubitane
ubitanne sskeleton,
keleton, w
hich proc
eeds via
via a “bridge
“bridge and
annd
which
proceeds
and
hass evolved
Key
ccut-strategy”
ut-strattegy” an
nd ha
evolved into
int
n o an
an enantioselective
enanntioselective approach
appproa
p
ch to
to 11.. K
ey sstep
tep iiss the
the
SmI2-m
-mediated
ediatted ccyclization
yclization of ann -carvonylgeraniol
-carrvonylgeraniol derivative
derivaative to
to the
the [8.2.2] bicycle
bicycle 6,
[5,6]
,6 ]
setting the
the stereochemistry
stereochemistry at
at C8.
C8.[5
Th
Thee sstrategy
trategy of the
the total
tot
o al synthesis
synthesis of (+)-cubitene
(+)-cubitene
setting
[7]]
[7
[8]]
being
n nine
nine steps
steps shorter
shorter than
thaan the
the benchmark
benchmarrk route,
route,[8
iiss now to
to be aadapted
dapted ttowards
owards
1, being
related
tthe
he re
lated ccalyculone
alyculone A ((2)
2) exhibiting
exhibi
b ting a challenging
challenging oxygenation
oxygeenaation pattern.
patttern.
P
arrazoaannthine A (4),
(4), iisolated
solatted ttogether
ogether w
ith ffour
oour re
lated ccompounds
ompounds ffrom
rom
r
tthe
he sea
Parazoanthine
with
related
Parazoanthus
aanemone
nnemonne P
arazoanthus axinellae
axinellaaee iinn 2009 by Thomas
Thomas and
anndd coworkers,
coworkers, contains
contains a rare
rarre
3,5disubs
u tituted hydantoine
hydaanntoine moiety
moiety with
with a non-alkylated
non-alkylated N3-position.
N3-position.[9]
3,5-disubstituted
Posters Session 2
In 20122 Manzo
Manz
n o et
et al.
al. published
published the
the first
first biomimetic
biomimetic synthesis
synthesis of 4.
4. Key
Key step
step of their
their
synthesis is
is the
the cyclization
cyclization of an
an open
open chain
chain precursor
precursor to
to yield
yield the
the hydantoin
hydaanntoin core.
core. [10]
synthesis
With
With regard
rega
garrd to
to their
their low
low yields
yields ann alternative
alternaative approach
appproach is
is under
unnder investigation.
investigaation.
References
References
[1
e fe r, K
imon, T.
T. Lindel,
Lindel, Phytochem.
Phhytochem. Rev.
Rev. 2013, 12,
12, 995-105.
5-105. [[2]
2] G
D. Prestwich,
P re s tw ic h , D
F. Wiemer,
W ie m e r,
[1]] J. W
Wefer,
K.. S
Simon,
G.. D.
D.. F.
einwald, J. C
lardy, J. A
m. Chem.
Chem. Soc.
Soc. 1978, 100, 2560-2561. [3]
[3] S. A.
A. Look,
Look, W.
W. Fenical,
Fenical, J. O
rg .
J. M
Meinwald,
Clardy,
Am.
Org.
Chem. 1982,
19982, 47,
47, 44129-4134.
129-4134. [4]
[4] M.-C.
M.-C. Lu,
Lu, N.-L.
N.-L. Le
e, S.-W.
S.-W. Tseng,
Tseng, J.-H.
J.-H. Su,
Su, Tetrahedron
Tetrahedron Lett.
Lett. 2011,
2011, 52,
Chem.
Lee,
5869-587
1. [5]
[5] E. Schöttner,
Schöttner, P.
P. Jones,
Jones, T. Lindel,
Lindel, Synthesis
Synthesis 2009, 33941-3956.
941-3956. [6]
[6] E. Schottner,
Schottner, M
5869-5871.
M..
Wi
echoczek
z , P.
P. G.
G. Jones,
Jones, T.
T. Lindel,
Lindel, Org.
Orrg. Lett.
Lett. 2010, 12,
12, 7784-787.
84-787. [7]
[7] K. Simon,
Simon, J.
J. Wefer,
W e fe r, E
h ö ttn e r,
Wiechoczek,
E.. Sc
Schöttner,
T. Lindel,
Lindel, An
gew . C
hem. 2012, 124
1047-11050. [[8]
8] M. Ko
dama, H. M
aeda, H. Hioki,
Hioki, Ch
em. Lett.
L e tt.
Angew.
Chem.
124,, 111047-11050.
Kodama,
Maeda,
Chem.
1996
09-810.
9
[[9
Cachet, G.
G. Genta-Jouve,
Gentaa Jouve, E.
E. L.
L. Regalado,
Regalado, R.
R. Mokrini,
Mokrini,, P
made, G.
G. Culioli,
Culioli,, O.
O. P.
P.
1996,, 8809-810.
[9]] N
N.. Cachet,
P.. A
Amade,
Th
omas, J.
J N
at. Pr
od. 2009, 72
612-11615. [10]
[10] E.
E. Manzo,
M anzo, D
Pagano, G
Nuzzo, M.
M. Gavagnin,
Gavagnin, M.
M. L.
L.
Thomas,
Nat.
Prod.
72,, 11612-1615.
D.. Pagano,
G.. Nuzzo,
Ci
avatta, Te
trahedron Lett.
Lett. 2012, 53
083-7084.
Ciavatta,
Tetrahedron
53,, 77083-7084.
255
P 191
Posters Session 2
ANTITUMOR POTENTIAL OF THE ZOANTHID Protopalythoa variabilis
Diego Veras Wilke1, Bianca Del Bianco Sahm1, Carlos Alberto M Rocha1,2, Ana
Isabel Vitorino Maia1, Otília Deusdênia Loiola Pessoa1, Letícia Veras Costa-Lotufo1
1
Federal University of Ceará, Coronel Nunes de Melo Street, 1127, 60.430-270, Fortaleza, Brasil.
2
Instituto Federal de Educação, Ciência e Tecnologia do Pará, Belém, Brasil
Our group has been studied the zoanthid Protopalythoa variabilis for its anticancer
potential. First we isolated two unusual lipidic alpha-aminoacids (LAAs) from the
hexane fraction, which showed high cytotoxicity against tumor cells. Further studies
showed that LAAs induce apoptosis on leukemia cells (Wilke et al., 2009 and 2010).
Since it was observed cytotoxicity among all the other fractions with different polarity,
it is expected that there is a great diversity of active compounds to be investigated from
this invertebrate. However, neither the further purification of the other fractions nor the
studies on LAAs mode of action were possible once their yield were very low. To
overcome this issue, currently, our efforts are focused on culturing P. variabilis
associated microorganisms. Ten strains were isolated and five of them yielded cytotoxic
extracts. The dereplication process of two extracts was conducted using AntiMarin
database. Piericidin A, Piericidin D and Glicopiericidin A were identified as the
cytotoxic agents of BRA035 extract. Piericidin A was isolated and inhibited tumor cell
growth in femtomolar range. BRA060 HRMS has at least thirty compounds, six of them
matched to nine cytotoxic compounds. Studies are in progress to confirm the identity of
BRA060 cytotoxic agents.
Posters Session 2
Support: CNPq, SISBIOTA-MAR, FUNCAP, CAPES.
256
P 193
Posters Session 2
ISOLATION AND ANTI-INFECTIVE ACTIVITY SCREENING OF MARINE
INVERTEBRATES-ASSOCIATED FUNGI
Diaa Youssef1, Lamiaa Shaala2, Fahad Al-Jamali3, Eric Schmidt4
1
King Abdulaziz University, Faculty of Pharmacy, 21589, Jeddah, Saudi Arabia
King Abdulaziz University King Fahd Medical Research Center, 21589, Jeddah, Saudi Arabia
3
Qatar University Faculty of Art & Science, Department of Biological and Environmental Sciences,
Doha, Qatar. 4University of Utah College of Pharmacy, Slc, 84112, United States
2
Posters Session 2
Filamentous fungi synthesize natural products that are often not found in other domains
of life, are structurally diverse, and are biomedically important. Fungi that are
associated with marine invertebrates or with algae are of growing importance as
promising sources of structurally unprecedented biologically active natural products. In
this study, 236 fungal isolates were purified from 14 different marine invertebrates
mostly sponges and tunicates that had been collected from the Red Sea. The antiinfective activity of 25 fungal extracts against several pathogens was evaluated.
Bioactivities against these pathogens for the most active 10 fungal isolates will be
presented. These results show a high diversity of fungi associated with marine
invertebrates as well as highlight their potential to produce anti-infective agents. Fungal
strains with proven activities were identified to the species level using the Internal
Transcribed Spacer ITS-rDNA sequences. Most of the active strains belong to the
genera Penicillium and Aspergillus.
258
Posters Session 2
P 194
NEW DIDEMNAKETALS FROM THE RED SEA MARINE TUNICATE
Didemnum SPECIES
Diaa Youssef1, Jihan Badr1, Gamal Mohamed1, Lamiaa Shaala2, Faida Bamane1
2
1
King Abdulaziz University, Faculty of Pharmacy, 21589, Jeddah , Saudi Arabia
King Abdulaziz University King Fahd Medical Research Center, 21589, Jeddah, Saudi Arabia
Didemnaketals are terpenoids which have been reported from a Palauan ascidian of the
Didemnum species by Faulkner’s group in 1991.1 So far, three compounds of this class,
didemnaketals A-C, were reported from the same species.1,2 Later on, the absolute
stereochemistry of the didemnaketals B and C was determined using a combination of
degradation and derivatization experiments, chiral shift methods, and comparison of
fragments to known compounds.3 Didemnaketals A and B inhibited the activity of HIV1 protease.1 Investigation of a fresh specimen of the Red Sea marine tunicate,
Didemnum species afforded two new didemnaketals, D and E. The new didemnaketals
differ from the reported ones in which that they lack the methyl functionality at C-6 and
the hydroxyl moiety at C-21. Instead, they possess either an ether or ester moiety at C-6,
in addition to new oxygen functionality at C-20 of the didemnaketals. The structure
determination of the new compounds was assigned by 1D and 2D NMR studies as well
as high-resolution mass spectral data. The biological activities of the compounds will be
presented.
References
1.
Posters Session 2
2.
3.
Potts, B. C. M.; Faulkner, D. J.; Chan, J. A.; Simolike, G. C.; Offen, P.; Hemling, M. E.; Francis,
T. A. J. Am. Chem. Soc. 1991, 113, 6321-6322.
Pika, J.; Faulkner, D. Nat. Prod. Lett. 1995, 7, 291-296.
Salomon, C. E.; Williams, D. H.; Lobkovsky, E.; Clardy, J. C.; Faulkner D. J. Org. Lett. 2002, 4,
1699-1702.
259
P 195
Posters Session 2
IISOLATION
SOLA
ATION O
OF
F BI
BIOLOGICAL
OLOGICAL A
ACTIVE
CTIVE A
ALGAL
LGAL C
COMPOUNDS
OMPOUNDS IINHIBITING
NHIBITING
TH
EA
CTIVITY OF
OF D
YNAMIN I
THE
ACTIVITY
DYNAMIN
D
iana Zaleta-Pinet
Zaalleta-Pinett1, M
Mauricio
au
a ricio Muñoz-Ochoa
Muñoz-Ochoa2, J. Iván
Iván Murillo-Alvarez
Murillo--A
Allvarez2, Phillip
Phillip J.
Diana
3
1
Robinson
Robiinson , IIan
an
an A. Van Altena
Alltena , Adam M
Mccluskey
ccluskeeyy1
1
The University
U iversity of
Un
of Newcastle,
Newcastle, Australia,
Australia, Chemistry
Chemistry - Th
Thee University
University of Newcastle,
Newcastle, 2308,
2308, Newcastle,
Newcastle,
Au
stralia.. 2Po
Politécnico
litécnico Nacional
Nacional (IPN)
(IPN) Interdiciplinary
Int
n erdiciplinary C
Center
enter ffor
or M
Marine
a rin e S
Sciences
ciences (Cicimar),
(Cicimar), T
Technology
echnology
Australia.
De
velopment, La
La Paz,
Paz, México.
México. 3T
The
he University
University of
of S
Sydney
ydney Children’s
Children’s M
Medical
edical R
Research
esearch Institute,
Institute, Cell
Cell
Development,
Signalling Unit,
Unit, Westmead,
Westmead, Nsw,
Nsw, 2145,
2145, A
u s tra lia .
Signalling
Australia.
E-m
mail: da
[email protected]
E-mail:
[email protected]
Posters Session 2
The
T
h dyn
he
ddynamin
naamin ssuperfamily
uperffamily iiss ccomprised
om
mpriised off di
different
fferentt sspecific
pecific an
and
ndd non
non-specific
-specific G
GTPase
TPase
[1]]
eenzymes.
nzymes.
s [1
These
These enzymes
enzymes play
playy pivotal
pivotal roles
roles in
in many
many
n cellular
cellular processes
processes including
including the
thhe
scission
division
during
resistance
scission of budding
budding vesicles,
vesicles, di
viision of organelles
orgaane
n lles duri
ng ccytokinesis
ytokinesis aand
nd re
sistannce ttoo
paathogenic infections.
inffections.[2] Recent
Recent re
reports
eports have
havve suggested
suggested that
thaat the
the inhibition
inhibition of the
the GTPase
GTPase
pathogenic
activity
activity of dynamins
dynam
mins may
may be a useful
u eful
us
u strategy
straategy to
to prevent
prevent different
different human
human pathologies,
patthologgies,
[3,4]
,4 ]
including
n cancer
canncer and
annd central
central nervous
nervoous system
system diseases.
diseases.[3
including
In the
thhe search
searrch for
for
o new
new dynamin
dynamin inhibitors,
inhibitors, we
we screened
screened 455 ethanolic
ethaannolic extracts
extracts obtained
obtained
from
r
alga
g e collected
collected along
along the
tthhe Pacific
Pacific coast
coast of Mexico
Mexico (8 Chlorophyta,
Chlorophyta, 18 Phaeophyta
Phaeophhyta
from
algae
annd 19 Rhodophyt
a). O
the screened
screeened eextracts,
xtracts, 21 (47
%) re
turned ssignificant
ignificannt dyna
min
and
Rhodophyta).
Off the
(47%)
returned
dynamin
inhibition
inhi
hibition
o levels
levels (90%)
(90%) at
at one or more
more off the
the
h three
thre
h e algal
algal extract
extract concentrations
concentraations
examined
algal
exaamineed (1.0, 0.1 and
annd 0.01 mg/mL).
mg/mL). A further
furt
u her nine
nine (20%)
(
algal extracts
extracts showed
show
wed
evidence
evidence off dynamin
dynaamin stimulation.
stimulattion.
Separation
the
and
Codium
Sepaarrattion of the
the active
active crude
crude extracts
ext
x racts from
from
r
the algae
algae Laurencia
Lauurencia pacifica
pacifica an
nd Cod
dium
simulans
simulanss resulted
resulted in
in several
several active
active fractions
fra
r ctions and
annd from
frrom them
the
h m the
the isolation
isolation of 8 pure
p
compounds.
compouunds. Six
Six of the
the pure compounds
com
o pounds were
were tested
tested for
for
o their
their biological
biological activity,
activi
v ty,
inhibition
inhibition
o of enzymes
enzymes dynamin
dynaamin I and
annd II as
as well
well as
as their
their anticancer
annticancer and
annd antibacterial
anntibacterial
activities.
activities.
References
References
1.
2.
3.
4.
260
Praefcke
P aefcke G.J.K.;
Pr
G .J .K .; M
McMahon
cMahon H.T.
H.T. Na
Nature
tu r e R
Rev.
ev. 2004, 5,
5, 1133-147.
33-1477.
U ruita R.;
Ur
R.; Henley
Henley JJ.R.;
.R .; C
ook T
.; M
ark A.
N. Proc.
Proc. Natl.
Natl. Acad.
Acad. Sci.
Sci. USA.
USA. 1997, 94,
94, 3377-384.
77-384.
Urruita
Cook
T.;
Mark
A.N.
Z chner S.;
Zu
S.; Noureddine
Noureddine M.;
M.; Kennerson
Kennerson M.;
M.; Verhoeven
Verhoeven K.;
K.; Claeys
Claeys K.;
K.; de
de Jonghe
Jonghe P.;
P.; Merory
Merory J.;
J .;
Zuchner
O iveira S.A.;
Ol
S.A.; Speer
Speer M.C.;
M.C.; Stenger
Stenger J.E.;
J.E.; Walizada
Walizada G.;
G.; Zhu
Zhu D.;
D.; Pericak-Vance
Pericak-Vance M.A.;
M.A.; Nicholson
Nicholson
Oliveira
G ; Timmerman
G.
Timmerman V.;
V.; Vance
Vance J.M.
J.M. Nat.
Nat. G
en. 2005, 37,
37, 2289-294.
89-294.
G.;
Gen.
B toun M.;
Bi
M.; Maugenre
Maugenre S.;
S.; Jeannet
Jeannet P.Y.;
P.Y.; Lacène
Lacène E.;
E.; Ferrer
Ferrer X.;
X.; Laforêt
Laforêt P.;
P.; Martin
Martin J.J.;
J.J.; Laporte
Laporte J.;
J .;
Bitoun
L chmüller H.;
Lo
H.; Beggs
B eggs A
.H.; Fardeau
F a rd e a u M
.; E
ymard B.;
B.; Romero
Romero N.B.;
N.B.; Guicheney
Guicheney P.
P. Nat.
Nat. Gen.
G en.
Lochmüller
A.H.;
M.;
Eymard
22005 37,
37, 11207-1209.
207-1209.
1209
2005,
Posters Session 2
P 196
STRUCTURE
S
TRUCTURE AND
AND FUNCTION
FUNCTIION OF
OF M
MONO
ONO A
AND
ND D
DIMERIC
IMERIC M
MEMBERS
EMBERS O
OF
F
D
ITERPENOIDS FROM
FROM THE
THE SOUTH
SOUTH CHINA
CHINA SEA
SEA CORALS
CORALS
DITERPENOIDS
W
en Z
hangg,,1 YueYue-Wei
Wei G
Guo,
uo,2 T
Tibor
iborr Ku
Kurtan,
rtaan,3 an
and
nd Raffaele
Raffaele Riccio
Riccio4
Wen
Zhang,
1
Research
R
esearchh Center
Center for
for Marine
Marine Drugs,
Drugs, School
School of
of Pharmacy,
Pharmacy, Second
Second Military
Military Medical
Medical Un
University,
iversity, 325 G
GuouoRoad, Shanghai
Shanghai 200433,
200433, P. R.
R. China.
China.2St
State
a te K
Key
ey Laboratory
Laboratory of
of Drug
Drug Research,
Research, Shanghai
Shanghai Institute
Institute of
of
He Road,
Materia Me
d ic a , C
h in e s e A
cademy of
of Sciences,
Sciences, 555
555 Zu
Zu Chong
Chong Zhi
Zhi Road,
Road, Zhang
Zhang Jiang
Jiang Hi-Tech
Hi -Tech Park,
P ark ,
Materia
Medica,
Chinese
Academy
Shanghai,
Shanghai, 201203,
201203, P.
P. R.
R. China.
China. 3De
Department
partment ooff Organic
Organic Chemistry,
Chemistry, Un
U
University
iversity of
of Debrecen,
Debrecen, P.O.B.:
P.O.B.: 20,
20,
H-401
Debrecen, Hungary.
Hungary. 4Di
Dipartimento
partimento ddii S
Scienze
c ie n z e F
Farmaceutiche
armaceutiche e Biomediche,
Biomediche, Via
Via Ponte
Ponte don
don
H-40100 Debrecen,
Melillo 884084
4084 Fisciano
Fisciano (SA),
(SA), Italy
Ita ly
Melillo
E-m
mail: we
n z h a n g 1 9 6 8 @ 1 6 3 .c o m
E-mail:
[email protected]
Posters Session 2
Corals
Cora
ls are
arre a rich
rich source
source of structurally
struucturally novel
novel nono and
annd dimeric
dimeric diterpenoids
diterpenoids with
with
ssignificant
ignificannt bioactivities.
bioactivities. The
The structural
struuctural complexity
complexity of coral
coraal diterpenoids
diterpenoids challenges
challenges the
the
cchemical
hemical ssynthesis
ynthesis and
and
n SAR
SAR studies.
studdies. This
This promotes
promotes a systematic
sysstematic investigation
investigattion on the
the
metabolites
m
etabbollites cconcerning
oncerning their
their chemistry
cheemistry and
and bioactivity,
bioactivity, leading
leading to
to the
the isolation
isolattion and
annd
different
kinds
diterpenoids
(including
dimer
sstructural
tructuraal eelucidation
lucidation of di
ffereent ki
nds of di
terpenoids
d (i
ncluding tthe
he di
mer of
diterpenoids,
di
terpenoi
n ds, namely
naamely biscembranoids).
biscembranoids). The
The structures
structures and
annd absolute
abbsolute configurations
conffigurattions were
were
determined
de
termine
n d by detailed
detailed sspectroscopic
pectroscopic aanalysis,
nnalysis, a modified
modiified mosher’s
mosher’s method,
method, and
annd
dichroism
(ECD)
timeeelectronic
lectronnic ssolution
olution aand
nd
n ssolid-state
olid-sttate ccircular
ircularr di
chroism (E
CD) ssupported
upported by ti
medependent
density
ECD
molecular
de
pendeent de
nsity ffunctional
uunctional ttheory
heory
o ((TDDFT)
TDDFT) E
CD ccalculations.
alcullattions. A sseries
eries of m
olecular
models
m
odels were
were established
estabblished and
annd can
can be used
used as
as ECD
ECD reference
reeference compounds
compounds in
in the
thhe
determination
de
terminat
n tion of absolute
abbsolute configuration
conffigura
g ation for
for
o their
their related
related derivatives.
derivattives. Some
Some reported
reported
sstructures
tructurees have
have to
to be revised.
revised. Potent
Potent tumor
tumor cell
cell growth
growth inhibitory
inhhibitory and
annd PTP1B
PTP1B inhibitory
inhibitory
metabolites
were
observed
SARs
were
Too
aactivities
ctivities
e of ssome
ome of tthe
he m
etabboolites w
ere obs
erved aand
nd ttheir
heir S
ARs w
ere sstudies.
tudies. T
understand
unde
rstand
n the
the mechanism
mechaannism of the
thee bioactivities,
bioactivities, a computational
computational method
method was
was employed
employe
o d
ttoo iinvestigate
nvestigatte tthe
he binding
binding mode
modee of the
the diterpenoids
diterpenoids with
with PTP1B
PTP1B enzyme
enzyme and
annd the
the
possible
pos
sible targets
tarrgets involved
involved in
in cancer
canncer processes,
processes, respectively.
respectively.
261
P 197
Posters Session 2
MARINE ALKALOID CLATHRODIN AS A POTENTIAL LEAD COMPOUND
FOR THE VOLTAGE-GATED SODIUM CHANNEL BLOCKERS
Ales Zula, Janez Ila , Danijel Kikelj
Faculty of Pharmacy, A kerceva Cesta 7, 1000, Ljubljana, Slovenia
Marine compounds with its unique structure and promising biological activity have
remained an interesting research area. A lot of attention is intended to pyrrole-2aminoimidazole alkaloids growing family (P-2-AI), which was isolated from different
sponges species and nowadays contains over 150 members. The structural simplest and
smallest members of the P-2-AI family are clathrodin and its brominated derivatives
oroidin and hymenidin, which are assumed to be the biosynthetic building blocks for
more complex members of the P-2-AI group.1 Clathrodin was first isolated from
sponges Agelas clathrodes in 1991 and in the biological test exhibited a broad spectrum
of bioactivity, where the blockade of voltage-gated sodium channels was the most
expressed. On isolated cells from the symphathetic ganglia of chicken embroys
clathrodin showed a blockade of voltage-gated sodium channels in the micromolar
range.2,3 Our purpose was to prepare clathrodin and evaluated on isolated voltage-gated
sodium channels and other targets. So far, two different total synthesis for clathrodin
have been published.4,5 We manage to prepare clathrodin by synthetic pathway which is
simple, green, scalable and has ability to produce oroidin, hymenidin and a set of
clatrodin’s derivatives. In the context of the research work the reactivity of double bond
in structure of clathrodin was also examined. NMR, HPLC, LC-MS analysis proved that
the presence of double bound in the structure contributes to the instability of clathrodin
in various solvents.
Posters Session 2
References
1.
2.
3.
4.
5.
262
Sullivan, J. D.; Giles, R. L.; Looper, R. E. Curr. Bioact. Compd., 2009, 40, 39-78.
Morales, J. J.; Rodriguez, A. D. The structure of clathrodin, a novel alkaloid isolated from the
caribbean sea sponge Agelas clathrodes. J. Nat. Prod., 1991, 54, 629-631.
Rentas, R. A. L.; Rosa, R.; Rodriguez, A. D.; De Motta, G. E. Effect of alkaloid toxins from
tropical marine sponges on membrane sodium currents. Toxicon, 1995, 33, 491-497.
Schroif-Gregoire, C.; Travert, N.; Zaparucha, A.; Al-Mourabit, A. Org. Lett., 2006, 8, 29612964.
Olofson, A.; Yakushijin, K.; Horne, D. A. J. Org. Chem., 1998, 63, 1248-1253.
Posters Session 2
P 198
FORMAL
F
ORMAL S
SYNTHESIS
YNTHESIS OF
OF ASPERGILLIDE
ASPERGILLIDE A FROM
FROM TRI-O-ACETYL
TRI-O-ACETYL DDG
LUCAL
GLUCAL
Andrea Zúñiga,
Zúñigga, M
Marcos
ar
a cos L.
L. Rivadulla,
Rivadu
a llaa, M
María
ar
a ía G
González,
onzállez, Generosa
Generosa Gómez,
Gómez, Yagamare
Yaagamar
ae
Andrea
Fall
Falll
De
partamento de
de Química
Química Orgánica,
Orgánica, Facultad
Facultad de
de Química,
Química, Un
iversidad ddee Vi
go, 36310,
36310, Vigo,
Vigo, Spain.
S p a in .
Departamento
Universidad
Vigo,
The A
The
Aspergillide
spe
p rgillide A (1)
(1) is
is a novel
novel 14-membered
14-membered macrolide
macrolidee recently
recently isolated
isolatted by kusumi
kusumi
aand
nnd cco-workers
o-workers1 from
from
r
a culture
culturee of Aspergillus
Aspe
p rgi
g llus os
ostianus
tianuss strain
strain 01F
01F313
313 iinn brom
bromineinemodified
an
m
odified 1/2PD
1/2PD medium.
medium. It was
was isolated
isolated from
from
r
an unidentified
unidentified marine
marrine sponge
sponge collected
collected
iinn P
ohnppei in
in 2001. This
This compound
compouund show
show significant
significant cytotoxic
cytot
o oxic activity
activity against
against murine
murine
Pohnpei
lleukemia
eukemia ccell
ell lline
ine L
1210.
L1210.
Here,
H
ere, we
we describe
describe a formal
form
o al total
tottal synthesis
synthesis of Aspergillide
Aspergillide A2 from
frrom the
the relatively
relattive
v ly
iinexpensive,
nexpens
n ive, commercially
commercially aavailable
vvailabble produc
ri-O-acetyl-D
D-glucal 5.
5. The
The retrosynthetic
retrosynthe
h tic
productt ttri-O-acetyl-D-glucal
ba
sis is
is outlined
outlined in
in Scheme
Scheme 1. Since
Since the
thhe conversion
conversion of 2 and
and
n 3 into
into 1 ha
lready be
bbeen
en
basis
hass aalready
re
ported in
in the
the literature
literatture3, we
we describe
describe only
only the
the preparation
preparrattion off compound
compound 2.
reported
The starting
start
r ing compound
compound 5,
5, was
was chosen
chos
h en because
becauuse it
it already
already contains
contains stereocenters
stereocenters 2 and
and
n 3
The
compound
p
4, and
and
n because
becaus
u e it
it was
was envisaged
envisaged as
as giving
giving access
access to
to compound
compound 4 through
throough
of compound
4,
the very
veryy efficient
efficient Claisen
Claisen rearrangement
rearrraanngement as
as the
the key
key step,
step, to
to achieve
achieve the
the stereocenters
stereocent
n ers
the
corresponding
molecule.
correspoonding to
to C3, C4 and
annd C7 of
of the
the target
tarrget m
olecule.
1.
2.
3.
Posters Session 2
References
References
K to, K.
Ki
kura, R.;
R.; Yoshida,
Yoshida, S.;
S.; Namikoshi,
Namikoshi, M.;
M.; Ooi,
Ooi, T.;
T.; Kusumi,
Kuusumi, T.
T. Org.
Orrg. Lett.
Lett. 2008,, 10,, 2225.
25.
Kito,
K.;; Oo
Ookura,
Z ñiga, A.;
Zú
A.; Pérez
Pérez M.;
M.; González
González M.;
M.; Gómez,
Gómez, G.;
G.; Fall,
Fall, Y.
Y. Synthesis
Synthe
h sis 2011, 20,
20, 33301.
301.
Zúñiga,
S bitha, G.;
Sa
G.; Reddy,
Reddy, D.V.;
D.V.; Rao,
Rao, A.S.;
A.S.; Yadav,
Yadav, J.S.
J.S. Tetrahedron
Tetrahedron Lett.
Lett. 2010, 51,
51, 44195.
195.
Sabitha,
Ackowledgement
A
ckowledgement
This w
This
work
ork was
was supported
supported financially
financially bbyy tthe
he X
Xunta
unta ddee Galicia
Galicia ((Nº
Nº EX
EXPTE.
PTE. C
CN
N 2012/184).
2 0 1 2 /1 8 4 ) . A
Andrea
ndrea Zúñiga
Zúúñiga
andd María
González
an
María G
onzález thank
thank the
the University
University of
of Vigo
Vigo for
for a Ph
Ph D fellowship.
fellowship.
263
P 199
Posters Session 2
MARINE DERIVED ACTINOMYCETALES ASSOCIATED TO SEDIMENTS
FROM MUSSEL RAFTS IN THE RIA OF PONTEVEDRA
Paz Zúñiga, Ana M Peñalver, Carlos De Eguilior, Santiago Bueno, Carmen
Schleissner, Fernando de la Calle, Carmen Cuevas
Microbiology R&D Dpt. PharmaMar SAU, Av. Los Reyes, 1 .ES-28770, Colmenar (Madrid). Spain
Posters Session 2
Drug discovery at PharmaMar to find new antitumoral microbial metabolites involves,
among other innovative technologies, selective marine sampling for the isolation of rare
actinobacteria.
The unusual habitat generated by bio-deposits of marine mussel cultures which produce
organic matter rich in C, N and S with traces of Cr, Cu, Fe, and Pb is expected to be an
extraordinarily rich source of new microorganisms, notably actinomycetes which are
theoretically very abundant in high content organic sediments.
Samples collected by scuba diving in the Ria of Pontevedra, were homogenized and
seeded on selective enriched media to target the growth of actinomycetales. DNA was
extracted from pure colonies using REP-PCR for molecular dereplication and partial
16S rRNA sequencing for taxonomy. All the unique strains were preserved in the
PharmaMar library of microorganisms.
A total of 676 strains were isolated from 8 sediment samples, corresponding to 179
Actinobacteria species belonging to 26 genera assigned to a half of the 14 known
Actinomycetales suborders: Corynebacterineae, Glycomycineae, Micrococcineae,
Micromonosporineae, Propionibacterineae, Streptomycineae and Streptosporangineae.
Although the vast majority belonged to the genus Streptomyces, a Salinibacterium strain
was also isolated. This rare genus has been described as a bacteria associated with cold
oceans (Artic and Antarctic). Specifically, the isolation of S. amurskyense has only been
described in Amursky Bay (East Sea). In addition, we also found two candidates for
possible new species of the Arcobacter and the Glycomyces genera.
These results demonstrate that the isolation protocols used by PharmaMar for targeting
actinobacteria in Ria Pontevedra are capable of finding unusual new biodiversity.
264
Posters Session 2
P 200
PROKARYOTIC M
PROKARYOTIC
MOLECULAR
OLECULAR A
ACTIVITY
CTIVITY P
PROFILING
ROFILING (PROMAP
(PROMAP)) A
AS
SA
PLATFORM
FOR
THE
DISCOVERY
OF
NOVEL
NATURAL
PRODUCT
P
L TFORM F
LA
OR TH
ED
ISCOVER
RY O
FN
OVEL
LN
ATURAL P
RODUCT
A
NTIBIOTICS
ANTIBIOTICS
W
eng Ru
hW
on
o g1, Allen
Alllen G.
G. Oliver
Oliver2 an
andd Roger
Rogger G.
G. Linington
Liningt
gtoon1
Weng
Ruh
Wong
1
Department
De
partment of
of Chemistry
Chemistry aand
nd B
Biochemistry,
iochemi
m s t r y, U
University
niversityy ooff C
California
alifforniaa S
Santa
anta Cruz,
Cruz, Santa
Santa Cruz,
Cruz, CA,
CA, 95064,,
US
A. 2Mo
Molecular
M
lecular Structure
Structure Facility,
F a c ility , D
Department
epartment ooff Chemistry
Chemistry and
and Biochemistry,
Biochemistry, University
University of
of Notre
Notre Dame,
D am e,
USA.
Notre
Dame,
USA.
Notre Da
me, IN
IN 46556,
46556, US
A.
E-mail:
[email protected]
Email: w
[email protected]
Posters Session 2
T
his sstudy
tudy
u eestablishes
stablishes a ne
w an
n ibiotic prof
nt
filing sstrategy
traategyy us
ing a pan
nel of 15 di
ddifferent
fferent
This
new
antibiotic
profiling
using
panel
cclinically
linically re
levaannt ba
cterial sstrains
trains
n ttoo ccreate
reate bi
ological ffingerprint
inggerprint profiles
proffiles for
foor all
all the
the major
major
relevant
bacterial
biological
cclasses
lasses of antibiotics.
antibiotics. We
We have
havvee recently
recently developed
developed a Prokaryotic
Prokaarryotic Molecular
Molecular Activity
Activity
Proffilingg (P
(ProMAP)
roMAP) platform
platform
o
that
tha
hat creates
creattes bi
biological
ological aactivity
ctivity ffingerprints
ingerprints of know
known
wn ttest
est
Profiling
ccompounds
ompouunds that
thaat is
is able
abble to
to cluster
clusster structurally
structurally similar
similar chemical
chemical ccompounds
ompounds based
baased on
biological
Wee ha
applied
bi
ollogiical ccharacteristics.
h racteriistics. W
har
hhave
avve ap
ppllied tthis
his technology
technol
h loggy to
to a marine
marriine natural
nattural products
products
d t
sscreening
creening
n library
librarry and
and identified
identified both
both known
known active
active compounds
compounds from
from
r
mixtture of
a mixture
cconstituents
onstitue
u nts without
without the
thhe need
need for
for
or prior
prior purification.
purificattion. Besides
Beside
d s accelerating
acceleraating natural
nattural products
products
dereplication
process,
will
de
replication proc
ess, this
this platform
plattform
o
will provide
provide detailed
detailed biological
biological characterization
chaara
r cterizaattion for
for
o
sscreening
creening
n libraries
librarries and
annd identify
identify high
high priority
priority natural
nattural products
p
produc
ts extracts
extracts for
for
o hit-to-lead
hit-to- lead
development.
de
velopment. In contrast
contrast to
to traditional
traditional antibiotic
anntibiotic screening
screeningg programs,
programs, which
which employ
employ
o blind
blind
bacterial
sscreening
creening
n of llarge
arge
r
llibraries
ibraarries aagainst
gainst sspecific
pecific ba
cterial ttargets,
arrgets, ffollowed
ol
o lowed by llaborious
abborious
deconvolution
de
convoolution and
annd structure
structure elucidation
elucidation of lead
lead compounds,
com
mpounds
p
s, the
the new
new ProMAP
ProMAP platform
plattform
o can
can
di
directly
rectly iidentify
dentify lead
lead compounds
compoundss with
with the
the highest
highest value
value as
as development
development candidates,
candidattes, even
even
complex
ffrom
rom
r
com
ompl
plex natural
nattural product
produc
d t extracts,
ext
x racts, and
anndd can
can be
b used
used to
to select
select either
eithe
h r broad
b d spectrum
broa
spectrum or
Gram-negative-specific
G
ram
m-neegattive-specific leads.
leads. Byy comparing
com
mpa
p ring the
the profiles
proffiles of bioactive
bioactive materials
materials across
across a
pa
annel off bacterial
bacterial pa
athogens it
it is
is possible
p sible to
pos
to create
create bioactivity
bioactivi
v ty profiles
proffiles that
thaat are
arre indicative
indicat
ative of
panel
pathogens
ccompound
ompouund class,
class, and
and to
to identify
identify that
thatt small
small number
number of structurally
struc
r turally and
and biologically
biologically novel
novel
llead
ead ccompounds
om
mpounds worthy
worthy of further
furt
u thher development.
development. These
These results
resul
u ts will
will provide
provide crucially
crucially needed
needed
llead
ead ccompounds
om
mpounds
p
for
o hit-to-lead
hit-to-lead antibiotic
anntibiotic development
development to
to address
address to
to growing
growing antibiotic
ant
n ibiotic
for
ccrisis.
risis.
265
Interior Partipants:Abstracts 18/08/13 22:49 Página 266
Participants index
Participants Index
Algeria
Denmark
Issam, Ferhi
Kildgaard, Sara
Maansson, Maria
Australia
Brkljaca, Robert
Garson, Mary
Mudianta, I Wayan
Quinn, Ronald
Rudd, David
Van Altena, Ian
Zaleta-Pinet, Diana
OC22, P19
P123
OC13
P156
P195
Austria
Grassauer, Andreas
L3
Belgium
Esguerra, Camila
Brazil
Costa-Lotufo, Leticia V.
Jiménez, Paula
Pessoa, Otilia
Rangel, Marisa
Torres, Maria
Wilke, Diego Veras
OC9
OC25
P142
P180
P191
Canada
Andersen, Raymond
Britton, Robert
IL1
OC21
China
Participants Index
Hong, Kui
Qian, Pei-Yuan
Zhang, Wen
IL6
P196
Colombia
Finland
Kiuru, Paula
Lillsunde, Katja-Emilia
Montalvão, Sofia
P91
P98
P121
France
Amade, Philippe
Bach, Stephane
Banaigs, Bernard
Bonnard, Isabelle
Bontemps, Nataly
Boufridi, Asmaa
Bourguet-Kondracki, M.-Lise
Creis, Emline
Gérald, Culioli
Goldstein, Solo
Grovel, Olivier
Hess, Philipp
Inguimbert, Nicolas
Legrave, Nathalie
Lesur, Brigitte
Mehiri, Mohamed
Meijer, Laurent
Mohamadi, Fahoullia
Othmani, Ahlem
Parrot, Delphine
Roullier, Catherine
Thomas, Olivier
Tomasi, Sophie
Tribalat, Marie-Aude
P8
P17
OC19
P33
P70
P74
OC18
OC6
P95
OC2
P118
P130
P133
P151, P152
P175
Georgia
Berrio Escobar, Jhon Fernando
Castellanos, Leonardo
Colorado Rios, Jhonny
Duque, Carmenza
Galeano, Elkin
Martínez Matamoros, Diana
Pastrana Restrepo, Manuel
Restrepo Espinosa, D. Carolina
Tello, Edisson
268
P90
P105
P14
P25, P26
P32
P47
P62
P113
P134
P143
P174
Nadiradze, Kakha
P181
Participants Index
Germany
Bogdanov, Alexander
Bruns, Hilke
Harms, Henrik
Hufendiek, Peter
Köck, Matthias
Koenig, Gabriele
Laatsch, Hartmut
Lindel, Thomas
Lohr, Friederike
Munoz, Julie
Schupp, Peter
Sirirak, Thanchanok
Wefer, Johannes
Italy
P16
P22
P78
P80
OC15
OC16
P92, P93
OC5
P100
P124
P162
P167
P190
Greece
Ioannou, Efstathia
Roussis, Vassilios
OC23, P81, P82, P83
IL9, P153, P154, P155
Hong Kong
P37
P38
IL7
P42
IL4
P68
P75
P107
P108
P128
P131
P63
Japan
Iceland
P99
Indonesia
Sinurat, Ellya
Israel
Ben-Hamo, Hilla
Kashman, Yoel
P24
P29
PL5
Jamaica
Gallimore, Winklet
Xu, Ying
Liu, Hongbing
Omarsdottir, Sesselja
Carbone, Marianna
Ciavatta, María Letizia
Ciminiello, Patrizia
Croci, Tiziano
Cutignano, Adele
Daniello, Filomena
D’Auria, Maria Valeria
della Sala, Gerardo
Fontana, Angelo
Gavagnin, Margherita
Guella, Graziano
Mancini, Ines
Manzo, Emiliano
Mollo, Ernesto
Nuzzo, Genoveffa
Pagano, Dario
P13
P88
Abe, Ikuro
Kaneko, Kensuke
Matsunaga, Shigeki
Okino, Tasufumi
Onodera, Ken-Ichi
Sakai, Ryuichi
Tanaka, Junichi
Tsukamoto, Sachiko
Uchimasu, Hajime
Wakimoto, Toshiyuki
P87
IL8
P129
P157
P171, P172
P182
P183
OC11
Ariffin, Siti Alwani
P7
Mexico
Rodríguez-Morales, Sergio
Sánchez-Rodríguez, Judith
Soria-Mercado, Irma E
P150
P159
P168
269
Participants Index
Malaysia
Participants Index
New Zealand
Slovenia
Blunt, John
Copp, Brent
Khalil, Iman
Liew, Lydia
Munro, Murray
Wang, Jiayi
Hodnik, Žiga
Zula, Ales
OC4
P89
P96
P189
Norway
Andersen, Jeanette
Hansen, Espen
Hanssen, Kine Østnes
Moldes-Anaya, Angel
Olsen, Elisabeth
Paulsen, Steinar
Sæther, Thomas
Svenson, Johan
OC24
P119
P69
P77
Participants Index
Portugal
Almeida, Celso
Barreira, Luísa
Brito, Ângela
Bruno de Sousa, Carolina
Costa Leal, Miguel
Custódio, Luísa
Gaspar, Helena
Gomes, Nelson
Martins, Ana
Martins, Rosário
Moreira-Silva, Joana
Pedrosa, Rui
Rodrigues, Maria João
Silva, Tiago H.
P3
P10, P11
P18
P21
OC20
P36
P67
P71
L4
P115
P122
P135, P136, P137
P145
P166
Reunion
Gros, Emmanuelle
P73
Saudi Arabia
El Gamal, Ali
Shaala, Lamiaa
Youssef, Diaa
270
South Africa
Beukes, Denzil
Bromley, Candice
Chiwakata, Maynard
Fakee, Jameel
Mavengere, William
P15
P20
P28
P51
P116, P117
South Korea
Kang, Heonjoong
Park, Seungil
Shin, Hee Jae
OC3
P132
P165
Spain
Panama
Gavilan, Ronnie
Gutiérrez, Marcelino
P79
P197
P50
P164
P193, P194
Albericio, Fernando
P1, P2
Alonso, Eva
P4
Álvarez, Mercedes
Álvarez Rodríguez, Susana
P5
Amat, Mercedes
P6
Aracil Mira, Jose
Asenjo Fernández, Fernando
Ávila Escartín, Conxita
Ballette, Roberto
P9
Benedit, Gonzalo
P12
Blasco, Jose María
Bueno Horcajadas, Santiago
Cañedo, Librada Mª
P23
Chousa, Olga
Coello, Laura
P30, P31
Cruz López, Patricia Gema
P34, P35
Cuevas, Carmen
de la Calle, Fernando
P39, P40
de Vera, Caterina R.
P41
Díaz Crespín, Guillermo
P43
Díaz-Marrero, Ana R.
P44
Domínguez Rodríguez, Humberto J.
P45
Domínguez Seoane, Marta
P46
Febles, Martin
P52
Fernández, Jose Javier
P54
Fernández, Rogelio
P55, P56, P57, P58, P59
Fernández Fernández, Javier
P53
Fernández Sousa, Jose María
L2
Francesch, Andres
P60
García Pindado, Julia
P64
Interior Partipants_Abstracts 24/09/13 10:25 Página 271
Participants Index
Sweden
Bohlin, Lars
Switzerland
Freeman, Michael
Li, Alicia
Morinaka, Brandon
Piel, Jörn
Thiessen, Alexander
Wilson, Micheal
P61
OC10
IL5
P192
Thailand
Chanthathamrongsiri, Naphatson
Musa, Vassana
Plubrukarn, Anuchit
P27
P126
P141
United Kingdom
Deng, Hai
Ebel, Rainer
Edrada-Ebel, Ruangelie
Florence, Gordon
Gao, Hong
Gu, Yucheng
Macintyre, Lynsey
Paterson, Ian
Tabudravu, Jioji
Viegelmann, Christina
Vinueza, Gabriela
P48
P49
IL10
P106
PL2
P187
P188
United States of America
Adams, Julián
Bernan, Valerie
Carter, Guy
De Brabander, Jef
Fenical, William
Gerwick, William
Hamann, Mark
Hughes, Chambers
Littlefield, Bruce
Molinski, Tadeusz
Moore, Bradley
Murphy, Brian
Romo, Daniel
Ruh Wong, Weng
Ziemert, Nadine
OC1
IL3
PL1
OC17
OC14
L1
PL4
PL3
PL6
OC8
P 200
OC12
271
Participants Index
García Ruiz, Cristina
P65
Garranzo, María
P66
González, Maria
P72
Gutiérrez, Agustín
P76
Hernández Daranas, Antonio
IL11
Herraiz Cobo, Jesús
Jiménez, Carlos
P84, P85
Just, Xavier
P86
Lamariano, Janire
P94
Lillo, Cristina
P97
Lois Rivadulla, Marcos
P101
Lombó, Felipe
Lorente, Adriana
P102, P103
Lorenzo, Paula
P104
Martín López, María Jesús
P109
Martínez Barrasa, Valentín
P111
Martínez Domínguez, Andrea
P112
Martínez Rodríguez, Mercedes
P114
Martín-Rodríguez, A. Jonatan
P110
Molina Guijarro, José Manuel
P120
Munt, Simon
IL2
Murcia, Carmen
P125
Norte Martín, Manuel
Núñez Pons, Laura
P127
Pelay Gimeno, Marta
OC7, P138
Peñalver, Ana
P139
Pérez Álvarez, Marta
P140
Reyes, Fernando
P144
Riguera Vega, Ricardo
Rodríguez, Jaime
P146
Rodríguez Acebes, Raquel
P147, P148, P149
Rodríguez de Lera, Angel
Sánchez-Amat, Antonio
P158
Schleissner, Carmen
P160, P161
Segade Parrado, Yuri
P163
Souto, María Luisa
P169
Spengler, Jan
P170
Tarazona, Guillermo
P173
Toledo Rodríguez, Christian C. P176, P177, P178, P179
Urda, Carlos
P184
Valderrama, Katherine
P185
Vaz Araújo, Belén
P186
Zúñiga, Paz
P199
Zúñiga Girón, Andrea
P198
Cubierta 4:Abstracts 01/08/13 20:01 Página 1
on Marine
Natural
Products
on Marine Natural Products
September 15th - 20th, 2013
La Toja Island, Galicia
Organized by:
Spain
Programme
and Abstracts

14th International Symposium on Marine Natural Products

Transcription

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