Overview
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ABSTRACT
The biodiversity of the marine environment together with its associated structurally diverse natural products have drawn the attention of research teams worldwide. Some 40 years of cumulative efforts have yielded six clinically useful approved drugs plus 30 agents in current clinical trials, from 25,000 discovered molecular entities. This article gives a current overview of marine-derived entities that have been EMA- and FDA-approved, their natural sources and their structural diversity. The main strategies used to overcome supply problems are also described.
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Mehdi BENIDDIR: Senior Lecturer in Pharmacognosy BioCIS, Pharmacognosy-Chemistry of Natural Substances team, Faculty of Pharmacy, Châtenay-Malabry, Université Paris-Sud, Université Paris-Saclay, France
INTRODUCTION
Natural substances from the plant kingdom and terrestrial micro-organisms (for example, morphine from poppies and penicillin G from the fungus Penicillium notatum) have long been considered the main source of active ingredients, for obvious reasons of ease of access and history of use. The considerable development of scuba diving since the end of the Second World War has enabled researchers to broaden their field of investigation to include an environment endowed with tremendous biodiversity. In addition to covering 71% of the earth's surface, the oceans alone are home to 34 of the 36 phyla that exist on planet Earth. The study of this biodiversity (red algae, sponges, ascidians and soft corals), which has mobilized a large number of academic and private research teams, has rapidly revealed an exceptional chemical diversity in terms of structural complexity (e.g. high degree of halogenation, high number of nitrogen atoms), with more than 25,000 chemical entities described today. Despite these numerous discoveries, obtaining sufficient quantities of an active compound - essential for validating the first preclinical studies - soon came up against problems posed by biological availability. To remedy this and succeed in developing drugs from the marine world, industrialists and academics had to redouble their ingenuity to cope with supply problems. These have included aquaculture, innovative chemical synthesis methodologies and bacterial fermentation. Today, the advent of the genomic era makes it possible to understand the conditions under which the molecule of interest is biosynthesized, and to characterize the actual producing organism, offering the prospect of industrially viable solutions to production problems.
After a brief description of the pharmaceutical portfolio related to marine-based medicines, this article details the various marine-based medicines currently used in therapeutics, as well as the – or – producing organization(s) (where these have been identified). Solutions deployed to overcome supply problems are also discussed.
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KEYWORDS
Marine natural products | marine invertebrate | supply problem
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Medicines from the sea
Bibliography
Websites
Alejandro Mayer, Medicines from the sea, the clinical portfolio: http://marinepharmacology.midwestern.edu/clinPipeline.htm (page consulted on April 12, 2017)
Patents
Gravelos DG, Lake R, Blunt JW, Munro MHG and Litaudon MSP. –Halichondrins: cytotoxic polyether macrolides. European Patent Office, Munich, Switzerland: Publication number EP 0, 572, p. A1 (1993).
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