Design and synthesis of novel substituted pyrazole as small molecule inhibitor of cytochrome P450 CYP121A1

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 3 compounds shows significant activity having MIC (6.25 µg/ml).

Keywords

• Mycobacterium tuberculosis
• Pyrazole
• CYP121A1
• Molecular docking