Synthesis, Biological Evaluation and Molecular Modeling Studies of Novel Tribromo-substituted Imidazole Analogs

Abstract

Introduction: With the increasing rate of antimicrobial resistance, there is an urgent demand of developing newer antimicrobial agents. In the present study we report a novel series of eighteen 1-(aryl)-2-(2,4,5-tribromo-1H-imidazol-1-yl)ethan-1-ones, which were synthesized and their spectral characterization was performed. The in-vitro studies of the compounds were carried out. Molecular modeling studies were performed on the most promising compound. The results obtained would help develop new compounds that may have broad-spectrum therapeutic effects. Methods: The compounds were synthesized by reacting the corresponding bromo-imidazoles with substituted phenacyl bromides. The predictive ADME studies, MM-GBSA studies, and In-vitro studies were carried out for all the compounds. Binding mode analysis of the most active compounds was carried out. DFT investigations were also performed. Results and discussions: All the synthesized compounds were found to be active against the different strains of microorganisms used in the in-vitro analysis. Binding mode analysis of the most active compounds were carried out in the active site of glucosamine-6-phosphate synthase (2VF5) and crystal structure of Mycobacterium tuberculosis InhA inhibited by PT70 (2X22). With the increasing global challenge of multi-drug resistance and the urgent need for new antimicrobial agents, these compounds show promising potential to meet emerging therapeutic demands in treating infectious diseases. © 2024 Elsevier B.V.