Synthesis of rotenoid derivatives with cytotoxic and topoisomerase II inhibitory activities

Abstract 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 IC 50 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.