Synthesis, DFT investigation, molecular docking analysis, ADMET studies, and biological evaluation of a novel series of imidazolidinone derivatives as potential antimicrobial agents

Abstract

In this study, we constructed twenty novel imidazolidinone derivatives via the reaction of 2-(methylthio)-3,5-dihydro-4H-imidazol-4-one derivatives (1a-c) with some active methylene reagents and nitrogen nucleophiles. The synthesized compounds were confirmed through spectral analysis such as 1H NMR, 13C NMR, FT-IR, and MS. Moreover, the synthesized compounds were optimized and utilizing the DFT/B3LYP/6-31(G) basis set to investigate their energies and the presence of two forms of isomers (E and Z). The results confirmed the stability of the E form. ADMET of new imidazolidinones was also studied to investigate their lipophilicity and Lipinski's rule for determination of their physiological biological analysis. Also, the antimicrobial activity of new compounds on Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, Streptococcus mutans, Candida albicans, and Aspergillus Nigar using the inhibition zone technique were evaluated. The results demonstrate that compound 11c showed higher activity rather than other compounds due to the presence of piperazine moiety out of the plane of the benzene ring. Additionally, the docking study showed an electrostatic bonding interaction of the hydrogen of 11c and the amino acids of two proteins such as PDBID: 3t88 and 2wje.