1,4-Diaryl-2-mercaptoimidazoles derivatives as a novel class of antimicrobial agents: design, synthesis, and computational studies

In search of a new class of potential antimicrobial agents, some 1,4-diaryl-2-mercaptoimidazoles (5a-5h) were prepared by employing a mild and green approach in which substituted anilines 3 were treated with phenacylbromide 2 in the presence of Na2CO3/K2CO3 followed by the treatment of a solid catalyst, p-TSA (para toluene sulphonic acid), to give imidazole derivatives in excellent yields. All compounds were characterized on the basis of their UV, IR, H-1 & C-13 NMR, and Mass spectral data. Pharmacotherapeutic potential with the possible molecular mechanism of action of the compounds were estimated on the basis of prediction of activity spectra for substances (PASS) prediction results obtained by PharmaExpert software. The activity profile predicted by PASS was further supported by some theoretical calculations, in vitro experimental evaluation, and then validated via docking studies. In vitro antimicrobial potential was evaluated via agar well diffusion assay against five bacterial strains (one Gram-positive and four Gram-negative bacteria) and two pathogenic fungi. The antibacterial activity of the test compounds 5a-h against P. aeruginosa was found to be similar to that of Ceftriaxone, an efficient second generation antibiotic. Compound 5h displayed promising broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacterial strains. Except 4e, almost all the compounds were found to have an excellent level of antifungal activity against C. albicans when compared with a standard drug, Fluconazole. The docking results obtained confirm the interactions of compounds (5a-h) with the active site of cytochrome P450 14 alpha-sterol demethylase. Thus, it is concluded that the compounds considered under this investigation have an excellent potential to be acted, as antimicrobial leads in the future medicinal chemistry.