School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan.
School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
Eur J Med Chem. 2020 Sep 1;201:112422. doi: 10.1016/j.ejmech.2020.112422. Epub 2020 Jun 6.
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 IC values to therapeutically attainable levels.
P-糖蛋白（P-gp）过表达是癌细胞获得多药耐药（MDR）表型的主要机制，与患者的临床预后不良相关。为了开发 MDR 逆转剂，我们合成并评估了一系列噻吩苯并呋喃衍生物（4-31）作为 P-gp 抑制剂，其中化合物 4、10 和 14 代表逆转 MDR 表型的最佳试剂。这些 P-gp 抑制剂在敏化人 ABCB1 过表达的 ABCB1/Flp-In™-293 细胞和 MDR KBvin 细胞方面比维拉帕米更为有效，对一系列化疗药物（包括长春新碱和紫杉醇）的敏感性增加了数倍，表现在各自的 IC 值降低到可治疗水平。
