A potent moiety of (E)-5-(4-(5-chlorothiophene-2-carbonyl) piperazin-1-yl)-N'-(substituted methylene) benzofuran-2-carbohydrazide: Molecular docking, synthesis and antimicrobial evaluation

Abstract

In this paper, we report new hybrid molecules of (E)-5-(4-(5-chlorothiophene-2-carbonyl) piperazin-1-yl)-N'-(substituted methylene) benzofuran-2-carbohydrazide (10a-10r) as an anti-microbial agent. The synthesized compounds have been characterized by FT-IR, Mass, ¹H and ¹³C NMR spectroscopic techniques and were evaluated on gram-positive (S. aureus and S. pyogenes), gram-negative (E. coli and P. aeruginosa) bacterial strain and fungal (C. albicans and A. Niger) strains by the broth dilution method. The compounds exhibited significant antibacterial and antifungal activities, out of which compounds 10b and 10o, having MIC 62.5 μg/mL, showed the best activity against gram-positive bacterial strain S. aureus. Furthermore, compounds 10e, 10j, and 10m, having MIC 62.5 μg/mL, showed the best activity against the gram-negative bacterial strain E. coli. In contrast, compounds 10g and 10n, having MIC 62.5 μg/mL, showed the best activity against gram-negative bacterial strain P. aeruginosa. Out of the series, compounds 10h and 10l have been found to possess better inhibitory activity with MIC 250 μg/mL, compared to standard drug Griseofulvin (MIC 500 μg/mL) against anti-fungal strain C. albicans. Additionally, the compounds were docked in DNA gyrase enzyme of gram-positive and gram-negative bacteria and also C. albicans fungal. Compounds 10h and 10l were docked with the CYP51 of C. albicans (PDB: 5V5Z), revealing that the benzyl ring of the carbohydrazide Schiff base formed a potent π-π stacking interaction with the Hem601 complex. Additionally, the carbonyl part of the amide functional group connecting the piperazine and thiophene rings was found to interact with His377 through a hydrogen bond, which is considered a significant interaction. The compounds are also checked for their drug-likeness property using Lipinski rule. On the basis of these findings, we can conclude that (E)-5-(4-(5-chlorothiophene-2-carbonyl) piperazin-1-yl)-N'-(substituted methylene) benzofuran-2-carbohydrazide is a potent antimicrobial agent against a variety of bacterial and fungal species.