CoMFA and CoMSIA Studies on Inhibitors of HIV-1 Integrase - Bicyclic Pyrimidinones

Abstract

To understand the structural requirements of HIV-1 integrase inhibitors and to design new ligands against human HIV-1 integrase with enhanced inhibitory potency, a 3D QSAR (quantitative structure-activity relationship) study with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a dataset of 35 bicyclic pyrimidinones which are inhibitors of human HIV-1 integrase was performed. QSAR models were computed with Sybyl. The 3D QSAR model showed very good statistical result, namely q², r² and r²_pred values were high for both CoMFA and CoMSIA. Based on the high values for q² and r² we are confident that the 3D QSAR model gives good predictions that may be used to design better HIV-1 integrase inhibitors. The CoMFA and CoMSIA models reveal that steric and electrostatic fields contribute significantly with biological activities of the studied compounds.