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 aminopeptidase-2 (Met AP-2). Bioassay-directed fractionation indicated that the activity was concentrated 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 1H and 13C NMR, DEPT, 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 compounds were cytotoxic to HeLa and B16F10 mammalian cells, with compound 1 showing strong activity against the B16F10 cell line.