QSAR and Molecular Docking Study of a Series of Combretastatin Analogues Tubulin Inhibitors

Abstract

In this article, we study a series of Combretastatin compounds which undergo B ring transformation. First of all, Genetic function analysis(GFA) is adopted to study two-dimensional quantitative structure activity relationship(QSAR). The results demonstrate that Apol, PMI-mag, Dipole-mag, Hbond donor, RadOfGyration descriptors make the most significant contributions to the activities of this series of inhibitors; Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis(CoMSIA) are adopted to study three-dimensional quantitative structure activity relationship, both of which demonstrate strong predictive abilities. The tri-dimensional contour maps of CoMFA and CoMSIA provide explanations for the structure-activity relationship of Combretastatin compounds, and elucidate the effects of different substituents of B ring on inhibiting the activities of tubulin polymerization. And molecular docking was used to analyze and validate quantitative structure activity relationship models. The results of this study provide evidence for further designing and synthesizing tubulin inhibitors and conducting structure optimization.KeywordsElectrostatic FieldQuantitative Structure Activity Relationship ModelMolecular Docking StudyCoMSIA ModelCoMFA ModelThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.