CoMFA and CoMSIA studies on thiazolidin-4-one as anti-HIV-1 agents

Abstract

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on thiazolidin-4-one class of compounds as HIV-1 reverse transcriptase (HIV-1 RT) inhibitors using global minima and crystal structure conformations. Results obtained from the crystal structure-based model yielded superior statistical data ( r cv 2 values of 0.683 for CoMFA and 0.678 for CoMSIA) when compared to those obtained by the global minima-based model ( r cv 2 values of 0.625 and 0.654 for CoMFA and CoMSIA, respectively). The models were validated using an external test set of 47 compounds. The predictive r 2 values for the crystal-based CoMFA and CoMSIA models were 0.735 and 0.739, respectively, while the corresponding predictive r 2 values for the global minima-based CoMFA and CoMSIA models were 0.654 and 0.635, respectively. 3D contour maps generated from these models provide the regions in space where interactive fields may influence the activity. The superimposition of contour maps on the active site of HIV-1 reverse transcriptase additionally helped in understanding the structural requirements of these inhibitors. The results provide insight for predictive and diagnostic aspects of this class of HIV-1 RT inhibitors for better activity.