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Novel imidazole derivatives as antifungal agents: Synthesis, biological evaluation, ADME prediction and molecular docking studies

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, 1 H-NMR, 13 C-NMR, and HRMS spectra and elem...

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Published in:Phosphorus, sulfur, and silicon and the related elements sulfur, and silicon and the related elements, 2019-09, Vol.194 (9), p.887-894
Main Authors: Altindag, Firuze Diyar, Saglik, Begüm Nurpelin, Acar Çevik, Ulviye, Isikdag, Ilhan, Özkay, Yusuf, Karaca Gençer, Hülya
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cited_by cdi_FETCH-LOGICAL-c338t-c77faebb2e3e4069d47fb8f35bcd1dd7c310f8ff2819451a0080d4a28e750b413
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container_title Phosphorus, sulfur, and silicon and the related elements
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creator Altindag, Firuze Diyar
Saglik, Begüm Nurpelin
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description 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, 1 H-NMR, 13 C-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 MIC 50 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.
doi_str_mv 10.1080/10426507.2019.1565761
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source Taylor and Francis Science and Technology Collection
subjects antifungal activity
Antifungal agents
Chemical synthesis
Cytochromes P450
Derivatives
dithiocarbamate
Fungi
Fungicides
Imidazole
Lead compounds
Molecular docking
NMR
Nuclear magnetic resonance
title Novel imidazole derivatives as antifungal agents: Synthesis, biological evaluation, ADME prediction and molecular docking studies
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