Discovery of a DNA Topoisomerase I Inhibitor Huanglongmycin N and Its Congeners from Streptomyces sp. CB09001

Huanglongmycin (HLM) congeners G–N (7–14) were isolated from Streptomyces sp. CB09001. Among them, 10–12 possesses a tricyclic scaffold with benzene-fused pyran/pyrone, confirmed by X-ray single crystal diffraction analysis of 12. The structure–activity relationship study of 1, 13, and 14 revealed not only the stronger cytotoxicity of 14 against tested cancer cells but also the critical role of the C-7 ethyl group of 14 in its binding to the DNA–topoisomerase I complex.