Caulibugulones A−F, Novel Cytotoxic Isoquinoline Quinones and Iminoquinones from the Marine Bryozoan Caulibugula intermis

An extract of the marine bryozoan Caulibugula intermis, collected in the Indo-Pacific off Palau, produced a distinct pattern of differential cytotoxicity in the National Cancer Institute's 60 cell line antitumor screen. Bioactivity-directed fractionation of the extract provided six new compounds, caulibugulones A-F (1-6). The structures of these novel metabolites were determined by spectrochemical analyses including LC-MS, HRFABMS, 1-D and 2-D NMR experiments, and by comparison with related compounds. The structures of compounds 2 and 3 were confirmed by chemical interconversion. The isolated compounds exhibited IC(50)'s of 0.03-1.67 microg/mL against murine tumor cells in an in vitro cytotoxicity assay.