2. Academic Validation
  3. Synthesis and biological evaluation of JL-A7 derivatives as potent ABCB1 inhibitors

Synthesis and biological evaluation of JL-A7 derivatives as potent ABCB1 inhibitors

  • Bioorg Med Chem. 2017 Aug 1;25(15):4194-4202. doi: 10.1016/j.bmc.2017.06.015.
Miaobo Pan 1,  Jian Cui 1,  Lei Jiao 2,  Hesham Ghaleb 1,  Chen Liao 1,  Jiaqi Zhou 1,  Mutta Kairuki 1,  Haiyan Lin 3,  Wenlong Huang 4,  Hai Qian 5
Affiliations

Affiliations

  • 1 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 2 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150000, PR China.
  • 3 Department of Biochemistry and Molecular Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, 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: ydhuangwenlong@126.com.
  • 5 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.
PMID: 28645831 DOI: 10.1016/j.bmc.2017.06.015
Abstract

Cancer chemotherapy failure is often due to the overexpression of ATP-binding cassette (ABC) transporters (particularly ABCB1), resulting in a variety of structurally and pharmacologically unrelated drugs efflux. The multidrug resistance (MDR) phenomenon could be reversed by ABCB1 inhibitors. Now, JL-A7 as the lead compound based on a triazol-N-ethyl-tetrahydroisoquinoline scaffold, 18 compounds were designed and synthesized. Substitution in para positions yielded high activities toward ABCB1. Moreover, compound 5 could effectively block the drug efflux function of ABCB1 and increase the accumulation of anti-cancer drugs to achieve effective treatment concentration in MDR cells.

Keywords

ABCB1 inhibitors; Cancer resistance; MDR; P-glycoprotein.

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