Synthesis and evaluation of mansonone F derivatives as topoisomerase inhibitors

A series of mansonone F (MF) derivatives were designed and synthesized. These compounds were found to be strong inhibitors for topoisomerases, with much more significant inhibition for topoisomerase II rather than topoisomerase I. The best inhibitor showed 20 times stronger anti-topoisomerase II activity than a positive control Etoposide. The cytotoxic activity of these MF derivatives was evaluated against human cancer cell lines CNE-2 and Glc-82, which showed that these compounds were potent antitumor agents. The structure–activity relationships (SARs) study revealed that o-quinone group and pyran ring are important for their cytotoxic activity.

Various novel mansonone F derivatives were designed and synthesized for SARs study, and some of these compounds showed significant stronger inhibition against topoisomerase II than a positive control Etoposide.Figure optionsDownload as PowerPoint slideHighlights
► A series of novel mansonone F (MF) derivatives were designed and synthesized.
► The derivatives with 7,8-dione and pyran ring were particularly important for their cytotoxic activity.
► Some of these compounds showed significant inhibition against topoisomerase II, which were 20-fold more potent than a positive control Etoposide.