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ZEBRA FISH IN RESEARCH

Ocean, the mother of origin of life, covers over 70% of the earth’s surface and hosts
approximately 87% of the Earth’s life (Hu et al., 2011). It is the source of unique chemical
compounds which are accumulated in living organisms as secondary metabolites meant for their
defence or communication signalling. These bioactive molecules may be convertible to drugs and
thus hold tremendous pharmaceutical potential. Pharmaceutical agents derived from treasure of
marine resources are chemotherapeutics, nutraceuticals and functional foods, analgesics and anti-
inflammatory, natural excipients, immunomodulators, cosmeceuticals, biotoxins etc. Among
these, researchers have extensively focused on marine originated chemotherapeutic drugs,
particularly anticancer, anti-TB and anti-HIV drugs, looking at their potential of being developed
as future therapeutics.
Marine genetic wealth is aptly described as ‘blue gold’. To date, more than 2.30 lakhs
marine species and isolation of more than 28,000 structurally unique bioactive compounds have
been documented. Sponges (37%), coelenterates (21%) and microorganisms (18%) are the major
sources of biomedical compounds followed by algae (9%), echinoderms (6%), tunicates (6%),
molluscs (2%) and bryozoans (1%) (Blunt et al., 2004). Marine organisms have more chemical
diversity as they evolved over a long period of time in severe and hostile marine environmental
conditions like freezing temperatures, high pressures, intense heat from hydrothermal vents and
perpetual darkness due to lack of sunlight (Ruth, 2006; Synnes, 2007). Two thumb rules can be
considered for marine biodiversity i.e. ‘high biodiversity means high chemical diversity’ and
‘habitat diversity equates to chemical diversity’.
At present, there are total 14 marine derived chemotherapeutic drugs which are either
approved or in pipeline i.e. under clinical trial phases (Mayer et al., 2010; Martins et al., 2014).
Cytarabine (anticancer) and vidarabine (antiviral) are antimetabolites and DNA polymerase
inhibitors developed from nucleic acid analogues, spongothymidine and spongouridine, derived
from the sponge Cryptotethya crypta. Trabectedin or ET-743 (Yondelis®), discovered from tunicate
Ecteinascidia turbinate, became the first marine-derived anticancer drug to reach the market
without any structural modifications and approved for the treatment of soft tissue sarcoma. It binds
to the DNA minor groove and interacts with proteins of the DNA repair machinery. Eribulin
mesylate, a halichondrin-B analogue which is approved for metastatic breast cancer, exhibits broad
anti-proliferative activity against tumour cells by binding to tubulin and arresting the cell cycle at
mitosis. Iota-carrageenan derived from red seaweed, is a potent antiviral agent which interferes with
the respiratory virus life cycle at a very early stage due to a physical mechanism of action.
Brentuximab vedotin is the latest marine drug to successfully enter into the market
approved for the treatment of Hodgkin and systemic anaplastic large cell lymphoma. It is based
on a synthetic analog of dolastatin-10 (monomethyl auristatin E) linked to an anti-CD30 antibody
(a cell membrane protein present on the surface of cancerous cells). Scientists have reported the
discovery of various antibiotics from marine resources. Remarkably, in January 2014, Indian
Council of Medical Research (ICMR) filed a patent on new promising antibiotic ‘transitmycin’
and claimed that it is effective against many pathogens including HIV and multiple drug resistant
strains of Mycobacterium tuberculosis (WIPO, 2015). SAU’s of Gujarat are not far behind in
exploration of marine resources. Recently, College of Fisheries Science (JAU), Veraval, has
successfully screened sea-weed extracts for antibacterial activity (Combined Agresco, 2015).
There are many challenges too in marine bioprospecting mainly including high
exploration cost (one million US dollar for 30 days), problem of supply, threat to marine
biodiversity, standardization of a commercial product, legal issues related rights (IPRs) etc. India,
blessed with coastline of about 7517 km and with identified 844 species of seaweeds, 486 species
of sponges, 218 species of corals, has great prospect in discovery of unexplored marine source of
drugs (Saravanan and Debnath, 2013).
In conclusion, countless marine organisms contain biochemical secrets that, if unlocked,
can provide new insights and understanding of molecular pharmacotherapeutics. Although large
numbers of novel compounds have been isolated from marine organisms and many of these
substances have pronounced biological activity, only very few have been converted into
chemotherapeutic drugs and marketed as pharmaceutical products.

References:
Blunt, J. W.; Copp, B. R.; Munro, M. H. G.; Northcote, P.T. and Prinsep, M.R. (2004). Marine
Natural Products. Natural Product Reports. 21: 1-49.
Combined Agresco (2015). In: Proceedings – 11th Combined Agresco Meeting (SAUs) – Animal
Health & Fisheries (7-9 April, 2015), AAU, Anand.
Hu, G. P.; Yuan, J.; Sun, L.; She, Z.G.; Wu, J. H.; Lan, X. J.; Zhu, X.; Lin, Y.C. and Chen, S.P.
(2011). Statistical research on marine natural products based on data obtained between
1985 and 2008. Marine Drugs. 9(4): 514-525.
Martins, A.; Vieira, H.; Gaspar, H. and Santos, S. (2014). Marketed marine natural products in the
pharmaceutical and cosmeceutical industries: Tips for success. Marine Drugs. 12(2):
1066-1101.
Mayer, A. M.; Glaser, K. B.; Cuevas, C.; Jacobs, R.S.; Kem, W.; Little, R.D.; McIntosh, J. M.;
Newman, D. J.; Potts, B. C. and Shuster, D. E. (2010). The odyssey of marine
pharmaceuticals: a current pipeline perspective. Trends in Pharmacological Sciences.
31(6): 255-265.
Ruth, L. (2006). Gambling in the deep sea. EMBO Reports. 7(1): 17-21.
Saravanan, A. and Debnath, D. (2013). Patenting trends in marine biodiversity: Issues and
Challenges. Pharma Utility. 7(4): 1-13.
Synnes, M. (2007). Bioprospecting of organisms from the deep sea: scientific and environmental
aspects. Clean Technology and Environmental Policy. 9: 53-56.
WIPO. (2015). A compound, transitmycin, effective against bacterial and viral pathogens. World
Intellectual Property Organization Patent Application no. WO 2015022698 A1. Available
at https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2015022698> accessed on
26th September 2015.

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