Chemistry and biology of bioactive natural products from marine and other sources

Marine micro- (dinoflagellates, bacteria, etc.) and macro-organisms (sponges, tunicates, etc.) collected in Okinawa are good sources of compounds with intriguing structures and interesting biological activities.

A potent cytotoxic macrolide from a dinoflagellate Amphidinium sp. was found to target actin cytoskeleton and covalently bind to Tyr200 of actin subdomain 4. Potent cytotoxic polyene macrolides from a tunicate Cystodytes sp. were found to be potent osteoclast inhibitors and to inhibit V-ATPase.

A hybrid molecule of caffeine and a β-carboline alkaloid from a tunicate Eudistoma sp. showed potent affinity for adenosine receptor A₃ subtype.

A natural immunosuppressant from a pathogenic actinomycete Nocardia brasiliensis targets amino acid transport system L existing on cell membranes and it is expected to be a lead compound of new immunosuppressants and anticancer drugs.

A number of novel fused-polycyclic alkaloids have been isolated from terrestrial plants of different species of the two genera Daphniphyllum and Lycopodium. Some of them are potent inhibitors of acetylcholine esterase and one of them is used as a supplement useful for memory improvement.

These bioactive natural products from marine and other sources are expected to be potential drug leads and useful bioprobes.

In this symposium, the structures and bioactivities of these interesting natural products will be described.