A fifteen year investigation of marine animal components as sources for new and potentially useful cancer chemotherapeutic drugs has led to our discovery of a number of such valuable substance. The especially productive Indian Ocean sea hare Dolabella auricularia has yielded (100 kg leads to or approximately 1 mg each) a series of very potent cell growth inhibitory substances designated dolastatins 1-9. The first 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 microgram/kg (T/C 240, to T/C 139 at 1.37 microgram/kg) in the National Cancer Institute's murine B16 melanoma. Structural elucidation of the new antineoplastic agents is underway, and recent progress is illustrated with peptide dolastatin 3 (P388 ED 50 2.7 x 10(-7) microgram/ml).
Steroid bufenolides resulting from epoxidation of the 17beta-2-pyrone ring of bufadienolides are rare. Five 20,21-epoxybufenolides, namely, 20S,21-epoxyresibufogenin (1), 20R,21-epoxyresibufogenin (2), 3-O-formyl-20S,21-epoxyresibufogenin (3), 3-O-formyl-20R,21-epoxyresibufogenin (4), and 3-oxo-20S,21-epoxyresibufogenin (5), were isolated from the Chinese toad skin extract drug Ch'an Su. The structures were elucidated by spectroscopic and chemical methods. The configuration at C-20 was assigned by the analysis of difference NOE spectra. The cancer cell (KB and MH-60) growth inhibition by the new 20,21-epoxybufenolides was examined, and 20,21-epoxides 1, 2, and 5 were found to significantly inhibit the leukemia MH-60 cell line.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.