Global Perspective

The name of the project relates to the beginning of researches in this area and a small symposium held In 1967 in Rhode Island, USA, with the ambitious title “Drugs from the Sea” which has endured over the decades as a metaphor for drug development from marine natural products.

Though early work onmarine compounds and their bio-evaluation had a remarkably high hit rates the first genuine drug from the sea was a long time coming.The report of Werner Bergmann in 1951 of unusual arabino and ribo-pentosyl nucleosides obtained from marine sponges collected in Florida, USA, led to the development of two anti-cancer nucleosides ara-A (vidarabine) and ara-C (cytarabine) which have been in clinical use for decades. Though, world widea large number of compounds have shown extreme promise as potential drugs, the actual approval as drugs and introduction in the market has not been easy and only a fewmarine derived compounds have been approved as drugs .

  1. Prialt (ω-conotoxin MVIIA) — a peptide originally from a tropical marine cone snail —approved in 2004 for the treatment of chronic pain in spinal cord injury.
  2. yondelis -from a tropical sea-squirt — was approved in october 2007 for the treatment of soft-tissue sarcoma.

However, the novel structural features of these marine sourced bio-actives have inspired further researches and some of these compounds have emerged as novel molecular tools to probe complex biological pathways and some such tools are listed below.

Product Application Original Source Method of Production
Okadaic acid Molecular probe phosphatase inhibitor Dinoflagellate Cell culture
Vent ® DNA polymerase Polymerase chain reaction enzyme Deep sea hydrothermal vent bacterium Recombinant protein
Green Fluorescent Protein (GFP) Reporter gene Bioluminescent jellyfish , Aequora victoria Recombinant protein
Formulaid ®(Martek Biosciences, Columbia, MD) Fatty acids used as additive in infant formula nutritional supplement Marine microalga Cell culture
Aequorin Bioluminescent calcium indicator Bioluminescent jellyfish, Aequora victoria Recombinant protein
Manoalide Molecular probe:phospholipase A2 inhibitor Marine sponge, Luffariella variabilis Wild harvest of sponge

Minute quantities isolated from marine sources have been the prime reason for their predominant evaluation in anti-cance, anti-fungal, anti-bacterial assays, and several marine compounds such as Bryostatin I , Dolastatin-10, Ecteinascidin 743, Dehydro-didemnin B [Aplidine] , , Kahalalide F , Discodermolide , Isohomo-halichondrin B , Thiocoraline, Isogranulatimide, Bengamide, Hemiasterelins A & B are being investigated by various pharma companies for anti-cancer properties.

The main challenge in sourcing new drugs from marine environment has been the extremely low quantities that can be isolated without impacting natural habitat. While the structural diversity of marine compounds make them ideal as lead molecules to pursue further synthetic options, theirdevelopment as drug candidate becomes a challange. yondelis for example has seen introduction in market only due to development of a synthetic strategy from a close natural structure. Following is a list of compounds being investigated for various activities.

Drug candidate Marine source Current status
Bryostatin 1 Bryozoans Clinical trials
Dolastatin Mollusc Clinical trials
Aplidin Tunicate Clinical trials
Kahalalide F Mollusc Clinical trials
Discodermolide Sponge Clinical trials
Isohomo-halichondrin B Sponge Pre-Clinical trials
Thiocoraline Micro-organism Pre-Clinical trials
Isogranulatimide Ascidian Licensed
Bengamide Sponge Clinical trials
Hemiasterlins A & B Sponge Licensed
girroline Sponge Licensed

Interest in drugs from marine sources has been primarily dominated by public funded researches and no pharmaceutical company has paid much attention to undertake explorative research in this area. Recently, a pan-European initiative “Pharmasea” has again reaffirmed the firm commitment of government funding agencies to this valuable area of exploratory research.