Design, synthesis and multidrug resistance reversal activity evaluation of 8-oxocoptisine derivatives.

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 10 μM 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.