P-Glycoprotein (P-gp) overexpression is a major mechanism by which cancer cells acquire the multidrug resistance (MDR) phenotype, and is associated with poor clinical outcome in patients. In an effort to develop MDR-reversal agents, we synthesized and evaluated a series of thiophenylbenzofuran derivatives (4–31) as P-gp inhibitors, among which compounds 4, 10, and 14 represented the optimal agent in reversing the MDR phenotype. These P-gp inhibitors were dramatically effective than verapamil in sensitizing the human ABCB1-overexpressing ABCB1/Flp-In™-293 cells and MDR KBvin cells to a series of chemotherapeutic agents, including vincristine and paclitaxel, as manifested by multi-fold decreases in the respective IC₅₀ values to therapeutically attainable levels.

P-糖蛋白（P-gp）的过度表达是癌细胞获得多药耐药性（MDR）表型的主要机制，并且与患者不良的临床预后相关。在努力开发MDR逆转剂，我们合成并评价了一系列thiophenylbenzofuran衍生物（的4 - 31），为P-gp的抑制剂，其中化合物4，10和14所表示的最佳剂逆转MDR表型。这些P-gp抑制剂在使人ABCB1过表达的ABCB1致敏方面比维拉帕​​米显着有效/ Flp-In™-293细胞和MDR KBvin细胞对一系列化学治疗剂（包括长春新碱和紫杉醇）的抗药性，其各自的IC ₅₀值降低了许多倍，达到了治疗可达到的水平。