Page 43 - 2023

Ph.D.
(Pharmacy)
DESIGN SYNTHESIS AND BIOLOGICAL EVALUATION OF
SOME SUBSTITUTED PYRAZOLE DERIVATIVES AS
ANTI-TUBERCULAR AGENTS
Ph.D. Scholar : Jasani Mitali Hardik
Research Supervisor : Dr. L. J.. Patel

Regi. No.: 18276011006
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.
Key words: Mycobacterium tuberculosis, Pyrazole, CYP121A1, Molecular docking,
MmpL3

18