2. Academic Validation
  3. Discovery of a series of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton as potential FAK inhibitors

Discovery of a series of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton as potential FAK inhibitors

  • Bioorg Med Chem. 2017 May 1;25(9):2593-2600. doi: 10.1016/j.bmc.2017.03.038.
Juan Sun 1,  Shen-Zhen Ren 2,  Xiao-Yuan Lu 2,  Jing-Jing Li 2,  Fa-Qian Shen 2,  Chen Xu 3,  Hai-Liang Zhu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China; Jiangsu Naique Biological Engineering Technology Company Limited, Zhenjiang 212415, PR China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: xuchn@nju.edu.cn.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China; Jiangsu Naique Biological Engineering Technology Company Limited, Zhenjiang 212415, PR China. Electronic address: zhuhl@nju.edu.cn.
PMID: 28363444 DOI: 10.1016/j.bmc.2017.03.038
Abstract

Focal adhesion kinase (FAK) is an important drug target that plays a fundamental role in mediating signal transduction system. We report herein the discovery of a novel class of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton with improved potency toward FAK. All of the 17 new synthesized compounds were assayed for the Anticancer activities against four Cancer cells, HepG2, Hela, SW116 and BGC823. Because of the combination of 1,4-benzodioxan, 1,3,4-oxadiazole and piperazine ring, most of them exhibited remarkable antitumor activities. Notably, compound 5m showed the most potent biological activities (IC50=5.78μM for HepG2, and IC50=47.15μM for SW1116), and its anti-FAK inhibitory activity (IC50=0.78μM) was also the best. Computational docking studies also showed that compound 5m has interaction with FAK key residues in the active site.

Keywords

Antitumor activity; Benzodioxan; FAK; Oxadiazoles; Piperazine.

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