DESIGN, SYNTHESIS, IN-VITRO AND IN-SILICO ANTIMYCOBACTERIAL ACTIVITY SCREENING OF NOVEL N?- [3-(SUBSTITUTED PHENYL AMINO) CHLOROACETYL]-4-(1H-PYRROLE-1-YL)-BENZOHYDRAZIDE DERIVATIVES

Ramu R. Naik and Pradeep Kumar M. R.*

ABSTRACT

In the present inquiry, *N′-[3-(substituted phenylamino) chloroacetyl]-4-(1H-pyrrol-1-yl) benzo-hydrazide* was reacted with various substituted primary amines to produce a new series of pyrrole derivatives. The synthesized compounds were thoroughly characterized using spectroscopic approaches, including IR, ¹H NMR, and ¹³C NMR, to establish their structural integrity. The antimycobacterial activity of these substances was tested against Mycobacterium TB strain H37Rv using the Microplate Alamar Blue Assay (MABA) technique. Among the studied compounds, R-2 and R-3 displayed high antitubercular activity, with a minimum inhibitory concentration (MIC) of 31.25 μg/mL, while R-1 and R-4 showed moderate activity, with an MIC of 62.5 μg/mL. To further study the binding interactions of these drugs with the M. tuberculosis enoyl-reductase (InhA) enzyme (PDB: 5JFO), in silico molecular docking experiments were done. The docking findings demonstrated high binding affinities, with compounds R-1, R-2, R-3 and R-4 having binding energies of -8.2, -7.6, -6.5, and -7.8 kcal/mol, respectively, confirming their potential as InhA inhibitors. These findings emphasise the prospective antitubercular capabilities of the synthesized pyrrole derivatives.

Keywords: Pyrrole, antimycobacterial activity, MABA method, 1H NMR and 13C NMR, tuberculosis.