Synthesis, Characterization, and Molecular Docking Study of Some Novel Imidazole Derivatives as Potential Antifungal Agents

Abstract

The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more effective antifungal agents. In this study, two novel series of imidazole derivatives containing dithiocarbamate (5a-5g) and (benz)azolethiol (6a-6n) side chains that are structurally related to the famous antifungal azole pharmacophore were synthesized, and the structures of them were characterized by spectral (IR, H-1 NMR, C-13 NMR, and MS spectra) analyses. The synthesized compounds were screened in vitro antifungal activity against pathogenic strains fungi. Theoretical ADME (absorption, distribution, metabolism, and excretion) predictions were calculated for final compounds. A molecular docking study of the most active compound with target "lanosterol 14 alpha-demethylase" (CYP51) was performed to unravel the mode of antifungal action. Compound 5e, which features imidazole and 4-methoxybenzyl piperazine scaffolds, showed the most promising antifungal activity with an MIC50 value of 0.78 mu g/mL against C. krusei. Effect of the compound 5e against ergosterol biosynthesis was observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. krusei.