One-pot synthesis, spectral characterization, biological evaluation, molecular docking studies and in silico ADME/Tox profiling of new 2,4,5 triaryl imidazole derivatives as anti tubercular agents

Abstract

BackgroundTuberculosis still looms large on the global epidemiological radar and warrants continuous effort in the direction of developing new anti TB drugs to battle evolving resistance mechanisms of the causative agent Mycobacterium tuberculosis. MethodsIn the present paper, synthesis of n has been attempted. All the synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR and Mass spectroscopy. Anti TB profile of the synthesized compounds were tested by MABA assay employing M.tb H37Rv strain. ResultsTwo compounds namely N-(2-acetoxy)-N-methyl-4-(4,5-diphenyl-1H-imidazole-2-yl) benzenamine and 2-(N-(4-(4,5-bis(4-methoxyphenyl)-1H-imidazole-2-yl)phenyl)-N-methylamino) ethanol exhibited impressive anti TB inhibitory potential with an MIC of 3.125 μg/mL. To visualize the binding interactions of the active compounds molecular docking studies were carried out on putative target M. tuberculosis Glutamine synthetase (MtGS) in complex with a trisubstituted imidazole. To ascertain their drug likeliness and safety profile in silico ADME/T prediction was performed on all the synthesized compounds. ConclusionThree compounds 1a, 2g and 2c exhibited good inhibitory potency against M.tb H37Rv and all the synthesized compounds also show promising antifungal activity.