Antibacterial study of 3-(2-amino-6-phenylpyrimidin-4-yl)-N-cyclopropyl-1-methyl-1H-indole-2-carboxamide derivatives: CoMFA, CoMSIA analyses, molecular docking and ADMET properties prediction

Because of the rapid increase in deaths due to Staphylococcus aureus (S. aureus) infection, significant resources have been invested over the past decade in new treatments. Successful therapy requires amalgam of therapies to delineate the pathogen while providing protection to the host cell. With this idea, indole-pyrimidine hybrids have been used to develop new antibacterial agents. This heterocyclic has a fundamental role in medicinal chemistry and serves as a key model for the development of various therapeutic agents including broad-spectrum antibacterial drugs. In this study, we have employed combined studies of Three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking which are validated by in silico ADME prediction; those methods have been performed on indole-pyrimidine hybrids against S. aureus. 3D-QSAR study was applied using Comparative Molecular Field Analysis (CoMFA) with Q(2) of 0.560, R-2 of 0.925, and Comparative Molecular Similarity Indices Analysis (CoMSIA) with Q(2) of 0.577, R-2 of 0.876. The predictive ability of these models was determined using a test set of molecules that gave acceptable predictive correlation (R-test(2)) values 0.729 and 0.737 of CoMFA and CoMSIA respectively. Developed models and Docking methods provide guidance to design molecules with enhanced activity. (C) 2018 Elsevier B.V. All rights reserved.