Synthesis and biological evaluation of thiophenylbenzofuran derivatives as potential P-glycoprotein inhibitors.

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Synthesis and biological evaluation of thiophenylbenzofuran derivatives as potential P-glycoprotein inhibitors.

Eur J Med Chem. 2020 Jun 06;201:112422

Authors: Hung CC, Chen CY, Wu YC, Huang CF, Huang YC, Chen YC, Chang CS

Abstract
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.

PMID: 32569926 [PubMed - as supplied by publisher]