Marine Animal Biosynthetic Constituents For Cancer Chemotherapy

Abstract

A 15 yr investigation of marine animal components as sources for new and potentially useful cancer chemotherapeutic drugs led to the discovery of a number of such valuable substances. The especially productive Indian Ocean sea hare Dolabella auricularia yielded (100 kg .fwdarw. .apprx. 1 mg each) a series of very potent cell growth inhibitory substances designated dolastatins 1-9. The 1st member of this new series, dolastatin 1, may represent the most potent anticancer agent so far uncovered with, e.g., a curative response (33%) using a dose of 11 .mu.g/kg (T/C [tumor/control] 240, to T/C 139 at 1.37 .mu.g/kg) in the National Cancer Institute''s murine B16 melanoma. Structural elucidation of the new antineoplastic agents is underway; recent progress is illustrated with the peptide dolastatin 3 ([mouse leukemia cells] P388 ED50 2.7 .times. 10-7 .mu.g/ml).