Biological activity, Molecular Docking Studies and Molecular Dynamics Simulations of 2,3,4,5-Tetrahydro-1H-pyrido[4,3-b] indoles as c-Met inhibitors

作者：Ye Lianbao^*; Wu Jie; Yang Jiebo; Chen Weiqiang; Luo Yan; Zhang Yanmei

来源：LATIN AMERICAN JOURNAL OF PHARMACY, 2016, 35(2): 416-420.

• biological activity
• c-Met inhibitors
• molecular docking
• molecular dynamics simulations
• molecular mechanism
• 2,3,4,5-tetrahydro-1H-pyrido[4,3-b] indoles

c-Met has been deregulated in many cancers and become one of the leading molecular targets in cancer. In our previous research, we designed and synthesized six novel 2,3,4,5-tetrahydro-1H-pyrido[4,3-b] indoles as c-Met inhibitors. In this study, we evaluated their biological activity at cellular and molecular level. The results showed that the majority of the compounds exhibited significant inhibitory effect on c-Met with IC50 values of 0.0145-0.5 mu M in TR-FRET-based assay and IC50 values of 1.34-34 mu M in cell-based assay. Furthermore, our docking experiments analyzed the results and explained the molecular mechanism of eminent activities to c-Met and molecular dynamics simulations method was then applied to perform further evaluation of the binding stabilities between the compounds 4a, 5a and their receptor 3dkf.

• 单位
  广东药学院