title: Insights through AM1 calculations into the structural requirement of N-hydroxythiosemicarbazone analogs as anti-tubercular agents.
abstract: Fujita-Ban, Hansch substituent constants, topological descriptors and conformational dependent descriptors were explored for quantification of anti-tubercular activity of N-hydroxythiosemicarbazone analogs. All the approaches gave statistically sound model which accounts for more than 88% of the explain variance against anti-tubercular activity except Fujita-Ban (approximately 75%). Fujita-Ban & Hansch approaches having certain limitation, however, another approache showed their significant role in explaining activity of the modified scaffolds. QSAR study of N-Hydroxythiosemicarbazone analogs furnished some important structural insights i.e., the R position is more prone for improving inhibitory activity and the R(1) position play a decisive role in the ionic interaction of the ligand with macromolecules. On the basis of findings, N-hydroxythiosemicarbazones interaction model with macromolecule of M. Tuberculosis has been proposed. These interactions might be helpful in further development of potent anti-tubercular agents.
authors.affiliation: Molecular Modelling Study Group, CADD Laboratory, Computational Chemistry Research, Department of Pharmacy, Shri G. S. Institute of Technology and Science, 23 Park RoadIndore, 452003, MP, India.
authors.forename: Revathi A
authors.initials: RA
authors.lastname: Gupta
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Gupta
authors.forename: Love Kumar
authors.initials: LK
authors.lastname: Soni
authors.forename: S G
authors.initials: SG
authors.lastname: Kaskhedikar
mesh_terms: D000465:Algorithms; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D013882:Thiosemicarbazones