Investigation of Quantitative Structure Activity Relationship of Isatin-based Oxadiazole Derivatives as Thymidine Phosphorylase Inhibitors

Abstract

To obtain a better understanding of chemical biological interaction of isatin-based oxadiazole derivatives as a thymidine phosphorylase (TP) inhibitor, 30 kinds of quantitative structure activity relationship (QSAR) models of isatin-based oxadiazole derivatives were established using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), respectively. Among them, the r 2 and q 2 of the best CoMFA model were 0.920 and 0.697, and the best CoMSIA model gave r 2 = 0.912 and q 2 = 0.692, respectively. Docking studies were used to find the actual conformations of chemicals in active sites of TP protease, as well as the binding pattern to the binding site in protease enzyme. The information provided by 3D-QSAR model and molecular docking offered useful references for the structural requirements of the 30 kinds of isatin-based oxadiazole derivatives and helped to design potential anti-tumor drugs of vascular inhibitors. Based on the 3D-QSAR model research and analysis of TP inhibitors, new TP inhibitors with higher activity were designed. Finally, molecular docking was used to verify the binding mode.