1,3,4-Oxadiazole derivatives as potential antitumor agents:discovery, optimization and biological activity valuation
Recent studies have proved that focal adhesion kinase (FAK) is a new potential therapeutic target in cancer therapy.In this study,a virtual screening was conducted to discover potential candidates for FAK inhibitors.Based on the results,a series of novel oxadiazole derivatives (5a–5q) bearing the benzotriazole group were designed and synthesized for FAK inhibitory evaluation.Among the compounds,5h,which has an ortho methoxy group on the benzene ring,exhibited the most potent inhibitory activity for cancer cell growth with an IC50 value of 11 μM and 0.250 μM against Hela cells and FAK,respectively.Further,the apoptosis assay indicated that compound 5h induced the apoptosis of HeLa cells,and docking simulation showed that 5h could bind to the FAK protein catalytic region.Taking these together,5h could be a lead for discovering novel FAK inhibitors.
Yin Luo Zhi-Jun Liu Guo Chen Jing Shi Jing-Ran Li Hai-Liang Zhu
State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing 210023,People”s Repu Department of Radiation Oncology,Emory University School of Medicine and Winship Cancer Institute of
国内会议
第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)
太原
英文
470-478
2018-05-01（万方平台首次上网日期，不代表论文的发表时间）