Abstract

Fifteen derivatives of 8-oxocoptisine were prepared based on that 8-oxocoptisine showed potent reversing effect against human cancer cells charactering multidrug resistance (MDR). The derivatives were evaluated for their growth inhibition and effects on reversing P-gp-mediated MDR against MCF-7/AMD cells. 12, 13-dinitro-8-oxocoptisine (6c), the most potential candidate with weak growth inhibition, significantly increased the sensitivity of adriamycin (ADM) against MCF-7/ADM cells by 213-fold at 10μM that was comparable to the reference compound verapamil. The preliminary structure-activity relationships (SARs) of these derivatives were discussed on the basis of the in vitro MDR reversal activities.

Keywords: Anti-cancer, MCF-7/AMD, multidrug resistance (MDR), 8-oxocoptisine, P-glycoprotein (P-gp), verapamil, MDR, Fumaria indica, breast cancer, chemotherapeutic agents