Two New Compounds Containing Pyridinone or Triazine Heterocycles Have Antifungal Properties against .

Antibiotics (Basel)

UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale U1285, University of Lille, F-59000 Lille, France.

Published: January 2022

Candidiasis, caused by the opportunistic yeast , is the most common fungal infection today. Resistance of to current antifungal drugs has emerged over the past decade leading to the need for novel antifungal agents. Our aim was to select new antifungal compounds by library-screening methods and to assess their antifungal effects against . After screening 90 potential antifungal compounds from JUNIA, a chemical library, two compounds, 1-(4-chlorophenyl)-4-((4-chlorophenyl)amino)-3,6-dimethylpyridin-2(1)-one (PYR) and ()--(2-(4,6-dimethoxy-1,3,5-triazin-2-yl)vinyl)-4-methoxyaniline (TRI), were identified as having potential antifungal activity. Treatment with PYR and TRI resulted in a significant reduction of bioluminescence as well as the number of fungal colonies, indicating rapid fungicidal activity. These two compounds were also effective against clinically isolated fluconazole- or caspofungin-resistant strains. PYR and TRI had an inhibitory effect on biofilm formation and reduced the thickness of the mannan cell wall. In a infection model, PYR and TRI decreased the mortality of nematodes infected with and enhanced the expression of antimicrobial genes that promote elimination. Overall, PYR and TRI showed antifungal properties against by exerting fungicidal activities and enhancing the antimicrobial gene expression of .

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773291PMC
http://dx.doi.org/10.3390/antibiotics11010072DOI Listing

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