title: Synthesis, antitubercular evaluation and 3D-QSAR study of N-phenyl-3-(4-fluorophenyl)-4-substituted pyrazole derivatives.
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.
authors: Department of Chemistry, Saurashtra University, Rajkot, Gujarat, India. drrckhunt12@yahoo.com
authors: R C
authors: RC
authors: Khunt
authors: V M
authors: VM
authors: Khedkar
authors: R S
authors: RS
authors: Chawda
authors: N A
authors: NA
authors: Chauhan
authors: A R
authors: AR
authors: Parikh
authors: E C
authors: EC
authors: Coutinho
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D007659:Ketones; D008956:Models, Chemical; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D007659:Ketones; D011720:Pyrazoles