Département de chimie moléculaire

The multidrug resistance protein 1 (MRP1), involved in multidrug resistance (MDR) of cancer cells, was modulated by verapamil, through stimulation of GSH transport, leading to apoptosis of MRP1-overexpressing cells. In this study, various iodinated derivs. of verapamil were synthesized, including iodination on the B ring, known to be involved in verapamil cardiotoxicity, and assayed for the stimulation of GSH efflux by MRP1. The iodination, for nearly all compds., led to a higher stimulation of GSH efflux. However, detn. of concomitant cytotoxicity is also important for selecting the best compd., which was 10-fold more potent than verapamil. This will then allow us to design original anti-cancer compds. which could specifically kill the resistant cancer cells. [on SciFinder(R)]