Synthesis of N'-(Substituted)-2-(4-(3-nitroimidazo[1,2-b]pyridazin-6-yl)piperazin-1- yl)acetohydrazides and their 1,3,4-Oxadiazole Derivatives: Characterization, Antimicrobial Activity and Molecular Docking Studies

Abstract

The growing pharmaceutical relevance of drug-resistant pathogens has necessitated the emergence of new treatment medicines. In this scenario, a novel series of N′-(substituted)-2-(4-(3-nitroimidazo[1,2-b]- pyridazin-6-yl)piperazin-1-yl)acetohydrazides and 1-(2-(substituted)-5-((4-(3-nitroimidazo[1,2- b]pyridazin-6-yl)piperazin-1-yl)methyl)-1,3,4-oxadiazol-3 (2H)-yl)ethan-1-ones have been synthesized and characterized by 1H & 13C NMR spectral data and screened for antimicrobial activity, as well as molecular docking studies. The synthesized compounds were tested against Escherichia coli (1668), Bacillus cereus (1272), Candida albicans (854) by using disc diffusion method. Among all the synthesized compounds 3c and 4c exhibit good potent antimicrobial activity against Escherichia coli, 3a, 4c against Bacillus cereus and 4a, 4c against Candida albicans. The Auto-Dock 4.2/ADT application was performed to investigate the binding interaction of the synthesized compounds with BAX protein. Among all the synthesized compounds 4e, 4a, 3e and 3a showed the highest binding affinity (-8.0, -7.5, -7.0 and -6.9 Kcal/mol) with BAX protein.