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.

中文翻译：

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设计，合成和评估一系列新型的逆转P-糖蛋白介导的多药耐药性的抑制剂

多药耐药性（MDR）仍然是通过化学疗法获得有效结果的主要障碍。需要发现新的化学逆转剂以克服MDR。我们的研究集中于通过点击化学获得具有三唑环具有MDR逆转能力的三唑环新药的更好方法。在20种已开发化合物中，与tariquidar和verapamil（VRP）相比，化合物19具有最小的细胞毒性作用，并且通过增加在K562 / A02细胞中的蓄积而显示出比VRP更高的逆转活性。化合物19在K562 / A02细胞中细胞内Rh123和阿霉素（DOX）积累的P-gp外排功能中也起着重要作用。此外，化合物19表现出约24小时的长寿命。这些结果表明，化合物19是设计用于克服癌症MDR的新药的潜在先导化合物。