Synthesis and primary evaluation of quinoxalinone derivatives as potent modulators of multidrug resistance

P-glycoprotein-mediated drug efflux from cells is believed to be an important mechanism in multidrug resistance (MDR) in cancer chemotherapy. The identification and development of P-glycoprotein inhibitors with high potency and low cytotoxicity holds great promise for overcoming MDR. A series of quinoxalinone derivatives were synthesized and evaluated primarily for their antiproliferative effect and MDR reversal activity in in vitro assay systems. Biological assays demonstrated that the compounds were, in general, endowed with good activity as P-glycoprotein inhibitors. Among them, compounds 10 and 16, which showed the highest MDR reversal activity without significant cytotoxicity, displayed potent P-glycoprotein inhibition activities and may be worthy of further research as potential adjunctive agents for tumor chemotherapy.