2. Academic Validation
  3. Structure-activity relationship study of novel 2-aminobenzofuran derivatives as P-glycoprotein inhibitors

Structure-activity relationship study of novel 2-aminobenzofuran derivatives as P-glycoprotein inhibitors

  • Eur J Med Chem. 2017 Jan 5:125:1023-1035. doi: 10.1016/j.ejmech.2016.08.044.
Chien-Yu Chen 1,  Chin-Min Lin 2,  Hui-Chang Lin 1,  Chien-Fu Huang 3,  Chih-Yu Lee 1,  Tze-Chun Si Tou 1,  Chin-Chuan Hung 4,  Chih-Shiang Chang 5
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, China Medical University, 91, Hsueh-Shih Road, Taichung 404, Taiwan, ROC.
  • 2 School of Pharmacy, College of Pharmacy, China Medical University, 91, Hsueh-Shih Road, Taichung 404, Taiwan, ROC; Department of Pharmacy, China Medical University Hospital, 2 Yude Road, Taichung 404, Taiwan, ROC.
  • 3 Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan, ROC.
  • 4 School of Pharmacy, College of Pharmacy, China Medical University, 91, Hsueh-Shih Road, Taichung 404, Taiwan, ROC; Department of Pharmacy, China Medical University Hospital, 2 Yude Road, Taichung 404, Taiwan, ROC. Electronic address: cc0206hung@gmail.com.
  • 5 School of Pharmacy, College of Pharmacy, China Medical University, 91, Hsueh-Shih Road, Taichung 404, Taiwan, ROC. Electronic address: chihshiang@mail.cmu.edu.tw.
PMID: 27810590 DOI: 10.1016/j.ejmech.2016.08.044
Abstract

Treatment of Cancer patients with chemotherapeutic drugs is often associated with the occurrence of tumors with a multidrug resistance (MDR). Furthermore, the relation between overexpression of P-glycoprotein (P-gp) and resistant cancers has been well established. In this study, novel 2-aminobenzofuran derivatives were synthesized and tested for their ability to modulate P-gp mediated multidrug resistance (MDR) in vitro. The most potent compound, 43, increased P-gp inhibitory activity at 5 μM by 11.12-fold and was 3.6-fold stronger than verapamil. Furthermore, 43 can sensitize Flp-In™-293/MDR cells toward vincristine, paclitaxel and doxorubicin by 17.95-fold, 13.68-fold and 26.43-fold at 2.5 μM, respectively. 43 also can sensitize the resistant Cancer cell line KBvin toward vincristine, paclitaxel and doxorubicin by 246.43-fold, 38.72-fold and 5.16-fold at 2.5 μM, respectively. In conclusion, important aspects for developing potent P-gp inhibitors have been emphasized in this study, providing a starting point for the further structural optimization of P-gp inhibitors.

Keywords

2-Aminobenzofuran; ABCB1; MDR; Multidrug resistance; P-glycoprotein; P-gp.

Figures