Synthesis, characterization, and antimicrobial analysis of 5-phenyl-4-((2-(piperazin-1-yl)ethyl)thio)-1,2,3-oxadiazole analogs through in vitro and in silico approach

1,3,4-Oxadiazoles and 1,2,3-oxadiazoles are well known heterocyclic compounds, which acts both as biomimetic and reactive pharmacophores. Many of them are key compounds with potential biological activities. A sequence of novel 1,2,3-oxadiazole derivatives having 2-[(piperazin-1-yl)ethyl]thio moiety were synthesized by multistep synthesis. The newly synthesized compounds were well characterized, and their antimicrobial activities were carried out by disk diffusion and broth dilution methods. Further, among the series of compounds 5a-l, compound 5f demonstrated a good inhibition against all the tested strains. Also, in silico analyses including molecular docking simulations, molecular dynamics simulations, and binding free energy calculations predicted that the compound 5f had an extensive and stable interaction with the target proteins. In addition, ADMET analysis also predicted that 5f demonstrated no toxicity and carcinogenicity. This makes 5f one of the potent antimicrobial agents which can be used as a potential drug in the near future. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

1,3,4-Oxadiazoles and 1,2,3-oxadiazoles are important heterocyclic compounds with potential biological activities. A series of novel 1,2,3-oxadiazole derivatives with antimicrobial activities were synthesized, among which compound 5f demonstrated good inhibition against all tested strains. In silico analyses predicted that compound 5f had extensive and stable interaction with target proteins, while ADMET analysis showed no toxicity and carcinogenicity, making it a potential drug candidate for the future.