2. Academic Validation
  3. Designed P-glycoprotein inhibitors with triazol-tetrahydroisoquinoline-core increase doxorubicin-induced mortality in multidrug resistant K562/A02 cells

Designed P-glycoprotein inhibitors with triazol-tetrahydroisoquinoline-core increase doxorubicin-induced mortality in multidrug resistant K562/A02 cells

  • Bioorg Med Chem. 2019 Aug 1;27(15):3347-3357. doi: 10.1016/j.bmc.2019.06.013.
Mutta Kairuki 1,  Qianqian Qiu 2,  Miaobo Pan 1,  Qifei Li 1,  Jiaqi Zhou 1,  Hesham Ghaleb 1,  Wenlong Huang 3,  Hai Qian 4,  Cheng Jiang 5
Affiliations

Affiliations

  • 1 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 2 School of Pharmacy, Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental Protection, Yancheng Teachers' University, Yancheng, PR China.
  • 3 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 4 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: qianhai24@163.com.
  • 5 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: jc@cpu.edu.cn.
PMID: 31202598 DOI: 10.1016/j.bmc.2019.06.013
Abstract

Multidrug resistance (MDR) refers to the cross-resistance of Cancer cells to one drug, accompanied by Other drugs with different mechanisms and structures, which is one of the main obstacles of clinical chemotherapy. Overexpression of P-glycoprotein (P-gp) was an extensively studied cause of MDR. Therefore, inhibiting P-gp have become an important strategy to reverse MDR. In this study, two series of triazole-tetrahydroisoquinoline-core P-gp inhibitors were designed and synthesized. Among them, compound I-5 had a remarkable reversal activity of MDR activity and the preliminary mechanism study was also carried out. All the results proved that compound I-5 was considered as a promising P-gp-mediated MDR reversal candidate.

Keywords

K562/A02 cells; Multidrug resistance; P-glycoprotein; Reversal activity.

Figures