3D-QSAR studies on thiazole derivatives as potent inhibitors of dihydroorotate dehydrogenase / 药物评价研究

ABSTRACT

Objective The three-dimensional quantitative structure activity relationship (3D-QSAR) method was applied to study thiazole derivatives as potent inhibitors ofdihydroorotate dehydrogenase,which provided useful guidance for more discovery of potent inhibitors of dihydroorotate dehydrogenase.Methods Molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to systematicly investigate 3D-QSAR of 38 hiazole derivatives as potent inhibitors of dihydroorotate dehydrogenase.Established models of CoMFA and CoMSIA and the predictive ability of models were validated.Three dimensional map was applied to analyzing the relationship between structure and activity of thiazole derivatives.Results The coefficients of cross validation q2 and non-cross validation r2 for CoMFA model were 0.796 and 0.978,and for CoMSIA model were 0.721 and 0.976 respectively.The prediction of activity of compound was close to the actual value of the two models.Effect of compound structure on its activity could be analyzed comprehensively and intuitively by three dimensional map.Conclusion The model reveals the relationship between the structure characteristics and the inhibitory activity,and has good predictive capability and stability to lay a good foundation for further development and research.