Synthesis, Molecular Docking and Biological Evaluation of 2-Mercaptomidazoles using Solid Phase Synthesis

Background: With the increasing resistance and side effects caused due to antifungal agents there is an urgent need for the new potent antifungal agents with low toxicity profile. Imidazoles have been used against fungal infections since long time. Further, our previous studies demonstrated that mercaptoimidazoles possessed good antifungal potency. Aim and Objective: This study was aimed to study the antifungal potency of new series of 2- mercaptoimidazoles. Materials and Methods: Eighteen new 2-mercaptoimidazoles containing substituted phenyl group were synthesized and structures of the synthesized compounds were characterized by spectral studies. The synthesized compounds were screened for their antifungal potency. Compound 2-(1-(3-hydroxyphenyl)-2- mercapto-1H-imidazol-4-yl)phenol was found to be the most potent compound among all synthesized compounds against tested fungal strains. Moreover, all the synthesized compounds were further subjected to molecular docking study for the inhibition of enzyme 14α-demethylase. Results: The in-silico molecular docking study results showed that all the synthesized compounds have minimum binding energy and good affinity for the active site and may be considered as good inhibitor of 14α-demethylase. Conclusion: 2-mercaptoimidazoles may be used as potential lead molecules as 14α-demethylase inhibitors.