title: 3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods.
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.
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.
authors.forename: V
authors.initials: V
authors.lastname: Aparna
authors.forename: J
authors.initials: J
authors.lastname: Jeevan
authors.forename: M
authors.initials: M
authors.lastname: Ravi
authors.forename: G R
authors.initials: GR
authors.lastname: Desiraju
authors.forename: B
authors.initials: B
authors.lastname: Gopalakrishnan
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D013938:Thymidine Monophosphate; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase