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

V Aparna; J Jeevan; M Ravi; G R Desiraju; B Gopalakrishnan

doi:10.1016/j.bmcl.2005.10.086

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

Bioorg Med Chem Lett. 2006 Feb 15;16(4):1014-20. doi: 10.1016/j.bmcl.2005.10.086. Epub 2005 Nov 15.

Authors

V Aparna¹, J Jeevan, M Ravi, G R Desiraju, B Gopalakrishnan

Affiliation

¹ School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.

PMID: 16290929
DOI: 10.1016/j.bmcl.2005.10.086

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents* / chemistry
Antitubercular Agents* / pharmacology
Computer Simulation
Crystallography, X-Ray
Drug Design
Models, Molecular*
Molecular Conformation
Mycobacterium tuberculosis / enzymology
Nucleoside-Phosphate Kinase / antagonists & inhibitors*
Quantitative Structure-Activity Relationship*
Thymidine Monophosphate* / analogs & derivatives
Thymidine Monophosphate* / chemistry
Thymidine Monophosphate* / pharmacology

Substances

Antitubercular Agents
Thymidine Monophosphate
Nucleoside-Phosphate Kinase
dTMP kinase