New monomeric and dimeric uridinyl derivatives as inhibitors of chitin synthase

• Published in: Bioorganic chemistry 2015-08, Vol.61, p.13-20
• Main Authors: Kral, Katarzyna, Bieg, Tadeusz, Nawrot, Urszula, Włodarczyk, Katarzyna, Lalik, Anna, Hahn, Przemysław, Wandzik, Ilona
• Format: Article
• Language: English
• Subjects: Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Aspergillus niger - drug effects; Candida albicans - drug effects; Chitin Synthase - antagonists & inhibitors; Chitin Synthase - metabolism; Chitin synthase inhibitors; Dimerization; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Microbial Sensitivity Tests; Rhizopus - drug effects; Saccharomyces cerevisiae - enzymology; Synergism; Uridine; Uridine - analogs & derivatives; Uridine - chemical synthesis; Uridine - pharmacology
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2015.05.007

[Display omitted] •New dimeric and monomeric amide derivatives of uridine have been synthesized.•Compound 7 showed activities against several fungal strains (MIC range 0.06–1.00mg/mL).•Compound 7 inhibited chitin synthase from Saccharomyces cerevisiae (IC50=0.8mM).•Compound 7 exhibited synergistic interaction with caspofungin against Candida albicans. This study described the synthesis and in vitro evaluation of eight new derivatives of uridine as antifungal agents and inhibitors of chitin synthase. Dimeric uridinyl derivatives synthesized by us did not exhibit significant activity. One of the studied monomeric derivative, 5′-(N-succinyl)-5′-amino-5′-deoxyuridine methyl ester (compound 7) showed activities against several fungal strains (MIC range 0.06–1.00mg/mL) and inhibited chitin synthase from Saccharomyces cerevisiae (IC50=0.8mM). Moreover compound 7 exhibited synergistic interaction with caspofungin against Candida albicans (FIC index=0.28).