New monomeric and dimeric uridinyl derivatives as inhibitors of chitin synthase

Bioorg Chem. 2015 Aug:61:13-20. doi: 10.1016/j.bioorg.2015.05.007. Epub 2015 May 22.

Abstract

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 0.06-1.00 mg/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).

Keywords: Antifungal agents; Chitin synthase inhibitors; Synergism; Uridine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Dimerization
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Microbial Sensitivity Tests
  • Rhizopus / drug effects
  • Saccharomyces cerevisiae / enzymology
  • Uridine / analogs & derivatives*
  • Uridine / chemical synthesis
  • Uridine / pharmacology

Substances

  • Antifungal Agents
  • Enzyme Inhibitors
  • Chitin Synthase
  • Uridine