design synthesis and biological evaluation of some substituted pyrazole derivatives as anti tubercular agents

Abstract

Discovering new drugs with novel targets is vital for the success of treatment of tuberculosis as antibiotic resistance is increasing among the TB population. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterium growth. Using a rational approach, that includes molecular docking studies of some substituted pyrazole derivatives a series of pyrazole analogue were designed and pass through computational studies. Compound with good docking score and ADME profile were synthesized using two step reaction and biologically evaluated for their inhibitory activity towards M. tuberculosis. All compounds were analyzed by IR, LCMS, 1H-NMR and 13C- NMR. Among them 5 compounds shows significant activity having MIC (3.12 to 6.25µg/ml). Synthesized compound were re-docked with MmpL3 protein to identify dual inhibitory approach. All synthesized compounds gives good docking score and shows dual inhibition acts on cellular metabolism and cell wall synthesis newline