Chemical investigations of marine cyanobacteria. The search for new anticancer agents from the sea

Abstract

Eighteen strains of marine cyanobacteria belonging to the genera Symploca and Lyngbya, which showed activity against multidrug resistant solid tumors, were examined for cytotoxins. This resulted in the isolation and identification of 11 known and 15 new secondary metabolites from extracts collected in Micronesia. The structures of these metabolites were determined through a variety of NMR techniques (TOCSY, HMBC, HSQC, COSY, ROESY, and NOESY) and/or chemical degradation. Most of the compounds isolated were of mixed peptide-polyketide biogenesis. The two most potent cytotoxins discovered were the depsipeptides palauʻamide and lyngbyastatin 3. The latter was shown to be a potent microfilament disruptor, but was poorly tolerated in vivo. Chemical degradation of the latter series of compounds demonstrated they were mixtures of epimers in the acid sensitive 4-amino-3-oxo-2,2· dimethylpentanoic acid unit, and not single compounds as recently suggested. Lyngbyastatin 3 and lyngbyabellin D are analogues of compounds isolated from the sea hare Dolabella auricularia. The isolation of lyngbyastatin 3 and lyngbyabellin D from marine cyanobacteria supports the proposal that many of the compounds isolated from this sea hare are of cyanobacterial origin.