Two- and three-dimensional QSAR studies on a set of antimycobacterial pyrroles: CoMFA, Topomer CoMFA, and HQSAR

Abstract

Designing compounds having good anti-tubercular activity is gaining much importance in the area of tuberculosis research due to the reemergence of antibiotic resistance strains. In this study, quantitative structure activity relationship (QSAR) of a group of 55 anti-tubercular agents with varying structures and potencies, CoMFA, Topomer CoMFA, and HQSAR studies have been performed on a series of antimycobacterial pyrroles. A training set containing 46 compounds served to establish the model and CoMFA was assessed by r 2 value of 0.852 and cross-validated the q 2 value of 0.614. In the Topomer CoMFA, r 2 was 0.805, whole cross-validated q 2 was 0.535. The predictive ability of CoMFA and Topomer CoMFA models was determined using a test set of 9 compounds, which gave the predictive correlation coefficients (r pred 2 ) of 0.623 and 0.458, respectively. HQSAR was also carried out as a complementary study, and the best HQSAR model was generated using atoms, bond, connectivity, and hydrogen atoms as fragment distinction, 7–10 as fragment size and three components showing the cross-validated q 2 value of 0.710 and conventional r 2 value of 0.795. CoMFA, Topomer CoMFA steric, electrostatic, and HQSAR atomic contribution maps were generated to analyze the structural features of the datasets on that govern their inhibitory potency. 3D and 2D-QSAR studies (CoMFA, Topomer CoMFA, HQSAR) of antimycobacterial pyrroles are described.