(1S-3aR-4S-6S-6aS-9aS-9bS)-9a-isocyano-6-(2-isocyano-2-methylpropyl)-1-4-dimethyl-7-methylidene-2-3-3a-4-5-6-6a-8-9-9b-decahydro-1H-phenalene and Leukemia-P388

Twenty-four metabolites derived from marine sponges were evaluated for their cytotoxicities against two human tumor cell lines, non-small cell lung carcinoma A549 and colon adenocarcinoma HT-29, and against one murine leukemia cell line, P-388, and evaluated for their ability to effect signal transduction in a newly developed cell adhesion assay using an EL-4 cell line. The compounds included latrunculin A [1], batzelline A [2], chondrillin [3], aureol [4], epihippuristanol, theonellamine B, discorhabdins A and C, kabiramide C, dercitin, meridine, manzamines A, B, and C, 8,15-diisocyano-11(20)-amphilectene and the corresponding C-15 formamide, a 20-carbon acetylenic alcohol, 4,5-dihydro-6"-deoxybromotopsentin, epispongiadiol, isospongiadiol, puupehenone, reiswigin A, and demethyl- and demethyloxyaaptamine. Latrunculin A [1], batzelline A [2], chondrillin [3], and aureol [4] expressed the desired profile of a greater than five-fold level of cytotoxicity against A549 relative to P-388, and an effect in the cell adhesion assay. In this group of compounds, cytotoxicity toward A549 was equal to or more pronounced than against HT-29. Latrunculin A was evaluated in an sc-implanted human A549 lung tumor xenograft mouse model and yielded a T/C of 146%. Batzelline A was evaluated in the cancer cell line panel at the National Cancer Institute and found to express selective cytotoxicity against several melanoma cancer cell lines.

Topics: Animals; Antineoplastic Agents; Cell Adhesion; Cell Division; Humans; Leukemia P388; Mice; Porifera; Protein Kinase C; Signal Transduction; Tumor Cells, Cultured