Amphimic acids and related long-chain fatty acids as DNA topoisomerase I inhibitors from an Australian sponge, Amphimedon sp.: Isolation, structure, synthesis, and biological evaluation

Article abstract of DOI:10.1016/S0040-4020(97)10099-0

Several C₂₇-C₃₀ unsaturated fatty acids have been isolated from an Australian sponge, Amphimedon sp., as human DNA topoisomerase I inhibitors. Three of them, amphimic acids A (1)-C (3), are unusual fatty acids possessing a cyclopropylidene group, and one is a new C₃₀ fatty acid 4. Their structures were elucidated by spectroscopic analysis and chemical degradation. The enantioselective synthesis of 1 was carried out to determine the absolute configuration of amphimic acids. The inhibitory activity of DNA topoisomerase I was evaluated for these natural products and synthetic derivatives.