Insights through AM1 calculations into the structural requirement of N-hydroxythiosemicarbazone analogs as anti-tubercular agents.
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.
Gupta
Revathi A
RA
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.
Gupta
Arun Kumar
AK
Soni
Love Kumar
LK
Kaskhedikar
S G
SG
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*
D000995:Antitubercular Agents; D013882:Thiosemicarbazones