Identification of Thiazoloquin(az)olin(on)es Derivatives as CD38 Inhibitors Through 3D-QSAR and Molecular Docking Simulations

Abstract

CD38 is regarded as a potential target. Inhibitors against CD38 can regulate calcium metabolism in human body to impede the occurrence of disease, including diabetes and myeloma. In this work, 47 thiazoloquin(az)olin(on)es analogues with high pIC50 values in the micromolar ranges are studied by three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking. The comparative molecule field analysis (i.e., CoMFA q2 = 0.790; r2 = 0.967; rpred 2 = 0.872) and comparative molecular similarity indices analysis (i.e., CoMSIA q2 = 0.723; r2 = 0.969; rpred 2 = 0.815) are applied. Then, the Topomer CoMFA method is performed to validate these models, and the results show that this model has q2 = 0.662, r2 = 0.915 and rpred 2 = 0.704. These results indicate that the three models have good predictive abilities. Subsequently, molecular docking highlights the important interactions between the ligand and the CD38 receptor protein. Keywords: 3D-QDAR, docking, CD38 inhibitor, Topomer CoMFA, CoMFA, CoMSIA