New cytotoxic manzamine alkaloids from a palaun sponge

A crude extract of a marine sponge showed initial inhibitory bioactivities in a yeast assay for inhibitors of methionine amino-peptidase-2, (Met AP-2) . Bioassay-directed fractionation indicated that the activity was concentra ted in the CH2Cl2-soluble fraction, and chromatography on silica gel led to the isolation of the two new bioactive alkaloids N-methyl-epi-manzamine D 1 and epi-manzamine D 2. The structures of the epi-manzamines were assigned by H-1 and C-13 NMR, DEFT, HMQC, and HMBC spectroscopy, and by comparison with the spectra of related compounds, and the structure of 1 was confirmed by X-ray structure analysis. Neither of the two isolated compounds showed selectivity in the yeast assay for inhibitors of Met AP-2, but both compoun ds were cytotoxic to HeLa and B16F10 mammalian cells, with compound 1 showi ng strong activity against the B16F10 cell line. (C) 2000 Elsevier Science Ltd. All rights reserved.