3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods

Three dimensional quantitative structure–activity relationship (3D-QSAR) studies were carried out on deoxythymidine monophosphate (dTMP) derivatives inhibiting thymidine monophosphate kinase (TMPK) in Mycobacterium tuberculosis. Molecular field analysis (MFA) models with three different alignment techniques, namely, least squares, pharmacophore based and receptor based methods were developed. Receptor based MFA model showed better results when compared with least squares and pharmacophore based models. The results help us to understand the nature of substituents required for activity and thereby provide guidelines to design novel and potent inhibitors as antitubercular agents.

Graphical abstractRobust and predictive 3D-QSAR models were developed for dTMP derivatives inhibiting TMP kinase. Three different alignment methods were used and compared with active site residues to explore the nature of substituent.Figure optionsDownload full-size imageDownload as PowerPoint slide