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

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Pharmacology

Background:

• Rising antifungal resistance and side effects necessitate novel antifungal agents with low toxicity.
• Imidazoles have a long history of use in treating fungal infections.
• Previous research indicated mercaptoimidazoles possess significant antifungal potency.

Purpose of the Study:

• To evaluate the antifungal potential of a new series of 2-mercaptoimidazoles.
• To explore their efficacy as inhibitors of the 14α-demethylase enzyme.

Main Methods:

• Synthesis and spectral characterization of eighteen novel 2-mercaptoimidazoles with substituted phenyl groups.
• Screening of synthesized compounds for antifungal activity against various fungal strains.
• In-silico molecular docking studies targeting the 14α-demethylase enzyme.

Main Results:

• Compound 2-(1-(3-hydroxyphenyl)-2-mercapto-1H-imidazol-4-yl)phenol exhibited the highest antifungal potency.
• Molecular docking revealed all synthesized compounds possess good binding affinity and minimum binding energy for the 14α-demethylase active site.
• The compounds are predicted to be effective inhibitors of 14α-demethylase.

Conclusions:

• The synthesized 2-mercaptoimidazoles demonstrate significant antifungal properties.
• These compounds show potential as lead molecules for developing new 14α-demethylase inhibitors.
• The findings suggest a promising therapeutic avenue for combating fungal infections.