Synthesis of rotenoid derivatives with cytotoxic and topoisomerase II inhibitory activities

6-Deoxyclitoriacetal (1) and a series of 11 further derivatives of it (2–12) were synthesized and evaluated for their cytotoxic and topoisomerase IIα inhibitory activities. Compounds bearing epoxide (2), morpholine (6) and benzylamine (10) moieties showed promising in vitro cytotoxic activities against four cancer cell lines, with IC50 values ranging from 0.38 to 0.73 μM. These three compounds also strongly inhibited topoisomerase II activity at 68.3–93.5% and showed a moderately high DNA intercalating property.

A novel series of 11 different 6-deoxyclitoriacetals that differ in the C11-OH substitution moieties were synthesized and biologically evaluated for anticancer activity. Compounds bearing epoxide (2), morpholine (6) and benzylamine (10) moieties showed promising cytotoxic activities against four cancer cell lines with IC50 values ranging from 0.45 to 0.73 μM, strongly inhibited topoisomerase II activity and showed a moderately strong DNA intercalating property.Figure optionsDownload as PowerPoint slide