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 (∼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 R₁ 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.

Keywords::

• Fujita-Ban approach
• Hansch substituent constant approach
• QSAR
• anti-tubercular
• N-Hydroxythiosemicarbazone analogs

Acknowledgements

The authors are grateful to the director of Shri G. S. Institute of Technology and Science, Indore for providing facilities for this work. The author R.A.G. is grateful to UGC, New Delhi, for providing junior research fellowship.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.