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Novel imidazole derivatives as antifungal agents: Synthesis,biological evaluation,ADME prediction and molecular docking studies
Authors:Firuze Diyar Altındağ  Begüm Nurpelin Sağlık  Ulviye Acar Çevik  İlhan Işıkdağ  Hülya Karaca Gençer
Institution:1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eski?ehir, Turkey;2. Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eski?ehir, Turkey;3. Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Anadolu University, Eski?ehir, Turkey
Abstract:Abstract

A series of 2-(substituteddithiocarbamoyl)-N-4-((1H-imidazol-1-yl)methyl)phenyl]acetamide derivatives was designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. All synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, and HRMS spectra and elemental analyses. Antifungal activity tests were performed against four different fungal strains. Molecular docking studies were performed to investigate the mode of action towards the fungal lanosterol 14α-demethylase, a cytochrome P450-dependent enzyme. ADME studies were carried out and a connection between activities and physicochemical properties of the target compounds was determined. Most of the final compounds exhibited significant activity against Candida albicans and Candida krusei with MIC50 value 12.5?μg/mL. The results of in vitro anti-Candida activity, a docking study and ADME prediction revealed that the newly synthesized compounds have potential anti-Candida activity and evidenced the most active derivative, 5b (2-Pyrrolidinthiocarbonylthio-N-4-((1H-imidazol-1-yl)methyl)phenyl]acetamide), which can be further optimized as a lead compound.
Keywords:Imidazole  dithiocarbamate  antifungal activity  molecular docking
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