New Antimicrobial Nitro Heteroaryl-1,3,4-Thiadiazole Derivatives Containing Piperazinyl Benzonitrile Moiety: Synthesis and in silico Study

Abstract

According to the antimicrobial activity of 1,3,4-thiadiazole compounds, a new series of derivatives was synthesized from the reaction of 5-nitro heteroaryl-1,3,4-thiadiazole with piperazinyl benzonitrile. The structure of the compounds was confirmed using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1HNMR), and mass spectral data. The antimicrobial activities of the synthetic compounds against bacterial strains (Staphylococcus aureus and Escherichia coli) and fungal strains (Candida albicans and Saccharomyces Cerevisiae) showed compound E as the best antibacterial compound. After that, the molecular docking of the compounds with Escherichia coli dihydroorotase (PDB ID: 2EG7) and Klebsiella pneumoniae (PDB ID: 4OR7) was studied using ArgusLab software, which showed low binding energies [Formula: see text][Formula: see text]Kcal/mol and [Formula: see text][Formula: see text]Kcal/mol, respectively. Finally, the prediction of their drug-likeness by the assessment of some physical and chemical properties such as hydrogen bond donor/acceptor properties, water solubility, lipophilicity and acute oral toxicity acknowledged their drug-like properties.