1. Synthesis, antitubercular evaluation and 3D-QSAR study of N-phenyl-3-(4-fluorophenyl)-4-substituted pyrazole derivatives.
- Author
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Khunt RC, Khedkar VM, Chawda RS, Chauhan NA, Parikh AR, and Coutinho EC
- Subjects
- Anti-Bacterial Agents pharmacology, Chemistry, Pharmaceutical methods, Drug Design, Humans, Hydrogen Bonding, Hydrophobic and Hydrophilic Interactions, Inhibitory Concentration 50, Ketones, Models, Chemical, Molecular Conformation, Static Electricity, Temperature, Antitubercular Agents pharmacology, Mycobacterium tuberculosis metabolism, Pyrazoles chemistry, Pyrazoles pharmacology, Quantitative Structure-Activity Relationship
- Abstract
As a part of our ongoing research to develop novel antitubercular agents, a series of N-phenyl-3-(4-fluorophenyl)-4-substituted pyrazoles have been synthesized and tested for antimycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv strain using the BACTEC 460 radiometric system. A 3D-QSAR study based on CoMFA and CoMSIA was performed on these pyrazole derivatives to correlate their chemical structures with the observed activity against M. tuberculosis. The CoMFA model provided a significant correlation of steric and electrostatic fields with the biological activity while the CoMSIA model could additionally shed light on the role of hydrogen bonding and hydrophobic features. The important features identified in the 3D-QSAR models have been used to propose new molecules whose activities are predicted higher than the existing systems. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antitubercular agents., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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