Synthesis, biological evaluation, and molecular docking studies of novel 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety as FAK inhibitors with anticancer activity

• Published in: Bioorganic & medicinal chemistry 2014-06, Vol.22 (11), p.2947-2954
• Main Authors: Duan, Yong-Tao, Yao, Yong-Fang, Huang, Wei, Makawana, Jigar A., Teraiya, Shashikant B., Thumar, Nilesh j., Tang, Dan-Jie, Tao, Xiang-Xiang, Wang, Zhong-Chang, Jiang, Ai-Qin, Zhu, Hai-Liang
• Format: Article
• Language: English
• Subjects: 2-Styryl-5-nitroimidazole derivatives; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dioxanes - chemistry; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases - antagonists & inhibitors; Focal Adhesion Protein-Tyrosine Kinases - metabolism; HeLa Cells; Humans; Molecular docking; Molecular Docking Simulation; Molecular Structure; Nitroimidazoles - chemical synthesis; Nitroimidazoles - chemistry; Nitroimidazoles - pharmacology; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.04.005

A series of 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety (3a–3r) has been designed, synthesized and their biological activities were also evaluated as potential antiproliferation and focal adhesion kinase (FAK) inhibitors. Among all the compounds, 3p showed the most potent activity in vitro which inhibited the growth of A549 with IC50 value of 3.11μM and Hela with IC50 value of 2.54μM, respectively. Compound 3p also exhibited significant FAK inhibitory activity (IC50=0.45μM). Docking simulation was performed for compound 3p into the FAK structure active site to determine the probable binding model. A series of 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety (3a–3r) has been designed, synthesized and their biological activities were also evaluated as potential antiproliferation and focal adhesion kinase (FAK) inhibitors. Among all the compounds, 3p showed the most potent activity in vitro which inhibited the growth of A549 with IC50 value of 3.11μM and Hela with IC50 value of 2.54μM respectively. Compound 3p also exhibited significant FAK inhibitory activity (IC50=0.45μM). Docking simulation was performed for compound 3p into the FAK structure active site to determine the probable binding model.