Benzofuro[3,2-d]pyrimidines inspired from cercosporamide CaPkc1 inhibitor: Synthesis and evaluation of fluconazole susceptibility restoration

Bioorg Med Chem Lett. 2018 Jul 15;28(13):2250-2255. doi: 10.1016/j.bmcl.2018.05.044. Epub 2018 May 23.

Abstract

In a context of growing resistance to classical antifungal therapy, the design of new drugs targeting alternative pathways is highly expected. Benzofuro[3,2-d]pyrimidine derivatives, derived from (-)-cercosporamide, were synthesized and evaluated as potential Candida albicans PKC inhibitors in the aim of restoring susceptibility to azole treatment. Co-administration assay of benzofuropyrimidinedione 23 and fluconazole highlighted a synergistic effect on inhibition of cell growth of a Candida albicans resistant strain.

Keywords: Antifungal activity; Benzofuro[3,2-d]pyrimidine; Candida albicans Pkc1; Cercosporamide; Fluconazole susceptibility restoration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / pharmacology*
  • Ascomycota / chemistry
  • Benzofurans / chemical synthesis
  • Benzofurans / pharmacology*
  • Biofilms / drug effects
  • Candida albicans / drug effects
  • Candida albicans / enzymology
  • Drug Resistance, Fungal / drug effects*
  • Drug Synergism
  • Fluconazole / chemical synthesis
  • Fluconazole / pharmacology
  • HeLa Cells
  • Humans
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / pharmacology*

Substances

  • Antifungal Agents
  • Benzofurans
  • Protein Kinase Inhibitors
  • Pyrimidinones
  • cercosporamide
  • Fluconazole
  • Protein Kinase C