ISOLATION, STRUCTURE DETERMINATION, AND BIOLOGICAL-ACTIVITY OF DOLASTATIN-12 AND LYNGBYASTATIN-I FROM LYNGBYA-MAJUSCULA SCHIZOTHRIX-CALCICOLA CYANOBACTERIAL ASSEMBLAGES

Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4), was isolated as an inseparable mixture with its C-15 epime r (1b) from extracts of a Lyngbya majuscula/Schizothrix calcicola asse mblage and a L. majuscula strain collected near Guam. Dolastatin 12 (2 a) was also encountered as an inseparable mixture with its C-15 epimer (2b) in L, majuscula/S. calcicola assemblages. At least one of the co mpounds in each mixture appeared to exist in solution as a mixture of slowly interconverting conformers resulting in broadened signals in H- 1 NMR spectra. Structure elucidation therefore relied principally on m ass spectroscopy and chemical degradation studies. Both 1ab and 2ab pr oved toxic with only marginal or no antitumor activity when tested aga inst colon adenocarcinoma #38 or mammary adenocarcinoma #16/C. Both 1a b and 2ab were shown to be potent disrupters of cellular microfilament networks.