Marine Molluscs As a Potential Drug Cabinet: an Overview
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Indian Journal of Geo-Marine Science Vol. 44(7), July 2015, pp. 961-970 REVIEW ARTICLE Marine molluscs as a potential drug cabinet: an overview Premalata Pati*, Biraja Kumar Sahu & R. C. Panigrahy Department of Marine Sciences, Berhampur University, Berhampur-760007, Odisha, India *[ Email: [email protected] ] Received 21 April 2014; revised 6 June 2014 Marine molluscs have emerged as an important source containing numerous unique secondary metabolites which could be used for development of new drugs against many communicable and non-communicable deadly diseases. The current status of biologically active compounds extracted, identified and isolated from marine molluscs and tested for their anti-cancer, anti-inflammatory and anti-microbial activities together with important compounds isolated from them such as Dolastatin 10 & 15, Kahalalide F, Keenamide A, Spisulosine-ES-285 etc. which possess anti-cancer and Ziconotide having anti-inflammatory properties are discussed in this paper. [Keywords: Marine molluscs, bioactive compounds, drugs] Introduction spread of many incurable and fatal diseases like As many as 34 phyla, of the total 36 known influenza, diabetes, coronary disorder, AIDS and animal phyla were reported from marine cancer globally. Again, many disease causing biosphere against 17 phyla from land1-4. The plant pathogens became drug resistant giving rise to components in sea contain all classes of algae (as their mutant forms. Coupled with such threat phytoplankton and seaweeds), angiosperms (sea perceptions and rapid fall in the availability of grasses and mangroves) and several species of land based natural resources, the scientists have fungus and an array of microbes (bacteria and shifted their research to marine environment virus). Marine organisms are used as nutritious which has been found as the hidden ground for a foods, animal feed, ornamental and recreational plethora of bio-molecules which can be used for items and also as potential source of marine discovery of new drugs. In fact, over 7000 natural natural products in health care since ancient times. products have been isolated from marine organisms2 so far and this number is increasing Benthos in the sea, live in most harsh and with addition of new products every day. The hostile physical environment being exposed to bioactive compounds having pharmaceutical extreme conditions of temperature, pressure, application were mainly derived from some salinity and often hypoxia and anoxia like microbes8-12, seaweeds4, 13-16, ascidians17,18 and situations. They are also susceptible to stiff sponges19-21. In addition, some valuable products competition for space, food, mate as well as from salmon and shark and lysate from the microbial infections. Since there is almost no Limulus had also contributed significantly to the scope for physical protection to escape from pharmaceutical industries22-24. Several products different hazards, they adapt themselves through with nutritional and pharmaceutical value such as complex biochemical processes and physiological Poly Unsaturated Fatty Acids (PUFA), β-carotene mechanisms. Synthesis of secondary metabolites etc.25 are now available in the racks of medical is their unique ability that helps them to protect shops and some more are in pre-clinical and against the ill effects of environmental hazards clinical trials. The recent research findings8-25 and microbial infections and many of these are, have further shown that many more species of off late found as promising source to meet the 5 marine organisms, particularly the molluscs, stand human health care demand . as a prospective source of valuable bioactive Exploration and exploitation of sea based compounds with great potential for new leads. resources have witnessed a paradigm shift in 6,7 Molluscs constitute an important group of recent years . The rapid increase in human animals in marine hydrosphere representing 23% population, change in their life style and climate of all the organisms. Since majority of these live change impacts have propelled the origin and 962 INDIAN J MAR SCI VOL 44, No.7, JULY 2015 in harsh and hostile intertidal rocky shores, anti-cancer, anti-inflammatory, anti-microbial mudflats and shelf zone exposed to a series of properties are discussed here. physical and chemical stresses, they are susceptible to wounds and damages caused by Anti-cancer compounds inter-species and intra-species competitions and Cancer is one of the very painful and deadly microbial attacks. These organisms therefore have diseases of public concern worldwide. Cases of the capability to adapt themselves and overcome cancer are on stiff rise causing several deaths different kinds of stress with the synthesis of every year. The World Health Organization secondary metabolites possessing immunological (WHO) has projected the cancer related deaths to 26 property and anti-microbial activity . A about 12 million by 2030, while American Cancer neurotoxin, having analgesic properties making it Society has projected 27 million new cancer cases 1000 times more potent than morphine without leading to 17.5 million deaths by 2050. Despite any side effects isolated from gastropod Conus tremendous developments in science and 27,28 magus shows the uniqueness of secondary technology, no effective medicine could be metabolites extracted from cone shells. Research developed so far for treatment of cancer. Present findings have further delineated the presence of cancer treatment is limited to surgical intervention many other secondary metabolites in molluscs that involves removal of infected body part and having anti-oxidant, anti-inflammatory, anti- application of chemotherapeutic drugs and 29-37 microbial and anti-tumour properties . In fact, radiation therapy to destroy and inhibit the 38 39 molluscan origin alkaloids , carotenoids and proliferation of cancer cells. None of these 40 conotoxins have been tested successfully for treatments actually cure cancer, but mostly only their strong bioactive characteristics. However lengthen the lifespan of a patient. Again all these studies pertaining to drug-discovery from them treatments, especially the chemotherapy and 41-44 remains under explored . radiation therapy are associated with many life Present study consists the current status of the threatening side effects. Therefore stride has been exploration and exploitation of bioactive made to trace new compounds to combat cancer. compound source from marine molluscs with due It has been established that natural products are emphasis to Indian coasts. It is hoped that it more effective in cancer treatments with would provide basic insight in the field of minimum side effects. According to WHO 80% of pharmaceutical discoveries from the molluscs the world's population especially living in from the sea in order to battle with the growing developing countries rely on plant-derived health issues in new millennium. medicines41. Global statistics further suggests that about 60% of drugs approved for cancer treatment Marine Mollusca and their significance are of natural origin and important among them are doxorubicin, daunomicin, bleomycin, Phylum mollusca were initially divided into 9 45 different classes of which two have been reported mytomicin-C, vincristine and vinblastine . as extinct. Of the seven extant classes, four have Oceans are now considered as treasure house of been labelled as major and three as minor phyla. bioactive compounds possessing anti-cancer (anti- The four major classes include Polyplacophora oxidant/cytotoxicity/anti-tumour) activity. During (Chiton, Katharina, Mopalia etc.), Gastropoda the last few decades, nearly 2500 new metabolites (Conch, Cones, Snails, Cypraea sp etc.), Bivalvia with promising anti-tumour property have been (Oysters, Clams, Mussels, Scallops etc.) and isolated and their effectiveness against cancer has Cephalopoda (Squids, Octopuses, Cuttlefish etc). been evaluated. The Food and Drug The three minor classes include Monoplacophora Administration (FDA) and those of the European (Neopilina), Solenogastres (Neomenia) and Agency for the evaluation of medicinal products Caudofoveata (Chaetoderma, Limifossor). Each have listed 113 drugs for cancer treatment during 1940 to 2010, in which only 2.65% are of marine of the extant molluscs supports some kinds of 46 economic activity. origin (Sawadogo et al., 2013) suggesting the need for more efforts, to utilise the marine Marine molluscs have been used in a variety resources in future. Marine molluscs stand as of ways; the most common being as a source of prospective candidates offering excellent food, ornaments and production of lime. A few opportunity to isolate anti-cancer compounds47. species act as scavengers in cleaning the Some important compounds of molluscan origin environment and pollution indicators (Mussel having convincing anti-cancer properties are watch programme). Of late, many molluscan given hereunder. species have been identified as superior source of secondary metabolites having wide range of Dolastatin 10 and Dolastatin 15: The linear pharmaceutical applications. Some important peptide Dolastatin 10 (Fig.1) and desipeptide compounds screened, isolated and tested for their Dolastatin 15 (Fig.2) have been isolated from the PATI et al.: MARINE MOLLUSCS AS A POTENTIAL DRUG CABINET: AN OVERVIEW 963 sea hare Dollabella auricularia of Indian Ocean. Kahalalide F: Kahalalide F (Fig.3) extracted They are found to have promising anti-cancer from Hawaiian mollusca Elysia rufescens is found properties48.