Design, synthesis and cytotoxic activity of novel spin-labeled rotenone derivatives

Three series of novel spin-labeled rotenone derivatives were synthesized and evaluated for cytotoxicity against four tumor cell lines, A-549, DU-145, KB and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tumor cell lines tested, with IC(50) values ranging from 0.075 to 0.738μg/mL. Remarkably, all of the compounds were more potent than paclitaxel against KBvin in vitro, and compounds 3a and 3d displayed the highest cytotoxicity against this cell line (IC(50) 0.075 and 0.092μg/mL, respectively). Based on the observed cytotoxicity, structure-activity relationships have been described.