Synthesis, biological evaluation and computational studies of pyrazole derivatives as Mycobacterium tuberculosis CYP121A1 inhibitors.

ABSTRACT: A series of imidazole and triazole diarylpyrazole derivatives were prepared using an efficient 5-step synthetic scheme and evaluated for binding affinity with Mycobacterium tuberculosis (Mtb) CYP121A1 and antimycobacterial activity against Mtb H37Rv. Antimycobacterial susceptibility was measured using the spot-culture growth inhibition assay (SPOTi): the imidazoles displayed minimum inhibitory concentration (MIC₉₀) in the range of 3.95-12.03 μg mL^-1 (10.07-33.19 μM) with 11f the most active, while the triazoles displayed MIC₉₀ in the range of 4.35-25.63 μg mL^-1 (11.88-70.53 μM) with 12b the most active. Assessment of binding affinity using UV-vis spectroscopy showed that for the imidazole series, the propyloxy (11f) and isopropyloxy (11h)

SUBMITTER: Alshabani LA 

PROVIDER: S-EPMC9667784 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature