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Design, synthesis and evaluation of a novel series of inhibitors reversing P-glycoprotein-mediated multidrug resistance.
Chemical Biology & Drug Design 2018 September
Multidrug resistance (MDR) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo-reversal agents is needed to overcome MDR. Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil (VRP) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells. Compound 19 also played an important role in the P-gp efflux function of intracellular Rh123 and doxorubicin (DOX) accumulation in K562/A02 cells. Moreover, compound 19 exhibited a long lifetime of approximately 24 hr. These results indicated that compound 19 is a potential lead compound for the design of new drugs to overcome cancer MDR.
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