title: Discovery of a series of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton as potential FAK inhibitors.
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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China; Jiangsu Naique Biological Engineering Technology Company Limited, Zhenjiang 212415, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Shen-Zhen
authors.initials: SZ
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Fa-Qian
authors.initials: FQ
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: xuchn@nju.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004146:Dioxanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057075:Enzyme Assays; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors*; D006801:Humans; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000625355:5-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)-3-((4-(3(trifluoromethyl)phenyl)piperazin-1-yl)methyl)-1,3,4-oxadiazole-2(3H)-thione; D000970:Antineoplastic Agents; D004146:Dioxanes; D010069:Oxadiazoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013871:Thiones; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: Antitumor activity; Benzodioxan; FAK; Oxadiazoles; Piperazine