Part F | 32
782 Part F Marine Derived Metabolites
32.4 Conclusions
Marine-derived fungi continue to be a prolific source
of new and novel bioactive secondary metabolites.
Some examples of bioactive marine natural products such as bryostatins obtained from macroorganisms are implicated by endosymbiotic microorganisms
as true producers. This notion has provoked marine
natural product chemists and pharmacologists to explore marine-associated fungi for interesting chemical entities that can be developed into drug candidates. The principle of implementing marine-derived fungi to produce bioactive secondary metabolites has resolved the main obstacle facing the development of marine-inspired pharmaceuticals, which
is that yields are limited, even through aquaculturing efforts. However, industrial fermentation of marine-derived fungi on a large scale will in future
enable the mass production of bioactive compounds,
which can be optimized to face market needs in
the case of the development of a marine-inspired
pharmaceutical.
The high productivity of marine-derived fungi has
attracted natural product chemists to invest more research effort in this area, aiming to find a new or novel
entity of bioactive natural product(s) that can be used as
milestones for developing new pharmaceuticals for the
treatment of serious ailments.
References
32.1
A.L. Harvey: Natural products in drug discovery,
Drug Discov. Today 13, 894–901 (2008)
32.2
T.F. Molinski, D.S. Dalisay, S.L. Lievens,
J.P. Saludes: Drug development from marine
natural products, Nat. Rev. Drug Discov. 8, 69–85
(2009)
32.3
A.M. Mayer, K.B. Glaser, C. Cuevas, R.S. Jacobs,
W. Kem, R.D. Little, J.M. McIntosh, D.J. Newman,
B.C. Potts, D.E. Shuster: The odyssey of marine
pharmaceuticals: A current pipeline perspective,
Trends Pharmacol. Sci. 31, 255–265 (2010)
32.4
S.S. Ebada, P. Proksch: Marine organisms and
their prospective use in therapy of human diseases. In: Nature Helps : : : . How Plants and Other
Organisms Contribute to Solve Health Problems,
ed. by H. Melhorn (Springer, Berlin, Heidelberg
2011) pp. 153–190
32.5
A.R. Duckworth, G.A. Samples, A.E. Wright,
S.A. Pomponi: In vitro culture of the ascidian
Ecteinascidia turbinata to supply the antitumor
compounds ecteinascidins, Aquaculture 241, 427–
439 (2004)
32.6
W. Bergmann, R.J. Feeney: Contributions to the
study of marine products. XXXII, The nucleosides of sponges. I, J. Org. Chem. 16, 981–987
(1951)
32.7
W. Bergmann, R.J. Feeney: The isolation of a new
thymine pentoside from sponges, J. Am. Chem.
Soc. 72, 2809–2810 (1950)
32.8
L. Zhang, R. An, J. Wang, N. Sun, S. Zhang, J. Hu,
J. Kuai: Exploring novel bioactive compounds
from marine microbes, Curr. Opin. Microbiol. 8,
276–281 (2005)
32.9
T. Mavromoustakos, T. Calogeropoulou, M. Koufaki, A. Kolocouris, I. Daliani, C. Demetzos,
Z. Meng, A. Makriyannis, J. Balzarini, E. De Clercq:
Ether phospholipid-AZT conjugates possessing
anti-HIV and antitumor cell activity. Synthesis,
conformational analysis, and study of their thermal effects on membrane bilayers, J. Med. Chem.
44, 1702–1709 (2001)
32.10
R. Yarchoan, R. Klecker, K. Weinhold,
P.D. Markham, H.K. Lyerly, D.T. Durack, E. Gelmann, S.N. Lehrman, R.M. Blum, D.W. Barry:
Administration of 3’-azido-3’-deoxythymidine,
an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex, Lancet
1, 575–580 (1986)
32.11
H. Mitsuya, R. Yarchoan, S. Broder: Molecular
targets for AIDS therapy, Science 249, 1533–1544
(1990)
32.12
J. Balzarini, G.J. Kang, M. Dalal, P. Herdewijn,
E. De Clercq, S. Broder, D.G. Johns: The antiHTLV-III (anti-HIV) and cytotoxic activity of 2’,3’didehydro-2’,3’-dideoxyribonucleosides: A comparison with their parental 2’,3’-dideoxyribonucleosides, Mol. Pharmacol. 32, 162–167 (1987)
32.13
R.F. Schinazi, C.K. Chu, A. Peck, A. McMillan,
R. Mathis, D. Cannon, L.S. Jeonq, J.W. Beach,
W.B. Choi, S. Yeola: Activities of the four optical
isomers of 2’,3’-dideoxy-3’-thiacytidine (BCH189) against human immunodeficiency virus type
1 in human lymphocytes, Antimicrob. Agents
Chemother. 36, 672–676 (1992)
32.14
B.M. Olivera, W.R. Gray, R. Zeikus, J.M. McIntosh,
J. Varga, J. Rivier, V. de Santos, L.J. Cruz: Peptide
neurotoxins from fish-hunting cone snails, Science 230, 1338–1343 (1985)
32.15
H. Terlau, B.M. Olivera: Conus venoms: A rich
source of novel ion channel-targeted peptides,
Physiol. Rev. 84, 41–68 (2004)
32.16
S.S. Ebada, R.A. Edrada, W. Lin, P. Proksch: Methods for isolation, purification, and structural elucidation of bioactive secondary metabolites from
marine invertebrates, Nature Protoc. 3, 1820–1831
(2008)
782 Part F Marine Derived Metabolites
32.4 Conclusions
Marine-derived fungi continue to be a prolific source
of new and novel bioactive secondary metabolites.
Some examples of bioactive marine natural products such as bryostatins obtained from macroorganisms are implicated by endosymbiotic microorganisms
as true producers. This notion has provoked marine
natural product chemists and pharmacologists to explore marine-associated fungi for interesting chemical entities that can be developed into drug candidates. The principle of implementing marine-derived fungi to produce bioactive secondary metabolites has resolved the main obstacle facing the development of marine-inspired pharmaceuticals, which
is that yields are limited, even through aquaculturing efforts. However, industrial fermentation of marine-derived fungi on a large scale will in future
enable the mass production of bioactive compounds,
which can be optimized to face market needs in
the case of the development of a marine-inspired
pharmaceutical.
The high productivity of marine-derived fungi has
attracted natural product chemists to invest more research effort in this area, aiming to find a new or novel
entity of bioactive natural product(s) that can be used as
milestones for developing new pharmaceuticals for the
treatment of serious ailments.
References
32.1
A.L. Harvey: Natural products in drug discovery,
Drug Discov. Today 13, 894–901 (2008)
32.2
T.F. Molinski, D.S. Dalisay, S.L. Lievens,
J.P. Saludes: Drug development from marine
natural products, Nat. Rev. Drug Discov. 8, 69–85
(2009)
32.3
A.M. Mayer, K.B. Glaser, C. Cuevas, R.S. Jacobs,
W. Kem, R.D. Little, J.M. McIntosh, D.J. Newman,
B.C. Potts, D.E. Shuster: The odyssey of marine
pharmaceuticals: A current pipeline perspective,
Trends Pharmacol. Sci. 31, 255–265 (2010)
32.4
S.S. Ebada, P. Proksch: Marine organisms and
their prospective use in therapy of human diseases. In: Nature Helps : : : . How Plants and Other
Organisms Contribute to Solve Health Problems,
ed. by H. Melhorn (Springer, Berlin, Heidelberg
2011) pp. 153–190
32.5
A.R. Duckworth, G.A. Samples, A.E. Wright,
S.A. Pomponi: In vitro culture of the ascidian
Ecteinascidia turbinata to supply the antitumor
compounds ecteinascidins, Aquaculture 241, 427–
439 (2004)
32.6
W. Bergmann, R.J. Feeney: Contributions to the
study of marine products. XXXII, The nucleosides of sponges. I, J. Org. Chem. 16, 981–987
(1951)
32.7
W. Bergmann, R.J. Feeney: The isolation of a new
thymine pentoside from sponges, J. Am. Chem.
Soc. 72, 2809–2810 (1950)
32.8
L. Zhang, R. An, J. Wang, N. Sun, S. Zhang, J. Hu,
J. Kuai: Exploring novel bioactive compounds
from marine microbes, Curr. Opin. Microbiol. 8,
276–281 (2005)
32.9
T. Mavromoustakos, T. Calogeropoulou, M. Koufaki, A. Kolocouris, I. Daliani, C. Demetzos,
Z. Meng, A. Makriyannis, J. Balzarini, E. De Clercq:
Ether phospholipid-AZT conjugates possessing
anti-HIV and antitumor cell activity. Synthesis,
conformational analysis, and study of their thermal effects on membrane bilayers, J. Med. Chem.
44, 1702–1709 (2001)
32.10
R. Yarchoan, R. Klecker, K. Weinhold,
P.D. Markham, H.K. Lyerly, D.T. Durack, E. Gelmann, S.N. Lehrman, R.M. Blum, D.W. Barry:
Administration of 3’-azido-3’-deoxythymidine,
an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex, Lancet
1, 575–580 (1986)
32.11
H. Mitsuya, R. Yarchoan, S. Broder: Molecular
targets for AIDS therapy, Science 249, 1533–1544
(1990)
32.12
J. Balzarini, G.J. Kang, M. Dalal, P. Herdewijn,
E. De Clercq, S. Broder, D.G. Johns: The antiHTLV-III (anti-HIV) and cytotoxic activity of 2’,3’didehydro-2’,3’-dideoxyribonucleosides: A comparison with their parental 2’,3’-dideoxyribonucleosides, Mol. Pharmacol. 32, 162–167 (1987)
32.13
R.F. Schinazi, C.K. Chu, A. Peck, A. McMillan,
R. Mathis, D. Cannon, L.S. Jeonq, J.W. Beach,
W.B. Choi, S. Yeola: Activities of the four optical
isomers of 2’,3’-dideoxy-3’-thiacytidine (BCH189) against human immunodeficiency virus type
1 in human lymphocytes, Antimicrob. Agents
Chemother. 36, 672–676 (1992)
32.14
B.M. Olivera, W.R. Gray, R. Zeikus, J.M. McIntosh,
J. Varga, J. Rivier, V. de Santos, L.J. Cruz: Peptide
neurotoxins from fish-hunting cone snails, Science 230, 1338–1343 (1985)
32.15
H. Terlau, B.M. Olivera: Conus venoms: A rich
source of novel ion channel-targeted peptides,
Physiol. Rev. 84, 41–68 (2004)
32.16
S.S. Ebada, R.A. Edrada, W. Lin, P. Proksch: Methods for isolation, purification, and structural elucidation of bioactive secondary metabolites from
marine invertebrates, Nature Protoc. 3, 1820–1831
(2008)