3-Phenyl-5-methyl-2H,5H-furan-2-ones: tuning antifungal activity by varying substituents on the phenyl ring

Bioorg Med Chem Lett. 2000 Aug 21;10(16):1893-5. doi: 10.1016/s0960-894x(00)00376-0.

Abstract

A series of racemic 3-phenyl-5-methyl-2H,5H-furan-2-ones related to a natural product, (-)incrustoporine, was synthesized, and their antifungal activity evaluated. The key structural feature, furanone ring, was closed via H2SO4-mediated cyclization of 2-phenylpent-4-enoic acids. The compounds displayed antifungal activity, especially against filamentous fungi. Expressed as the minimum inhibition concentration (MIC) in micromol/L, the activity of the most promising derivative against Absidia corymbifera matched that of ketoconazole (31.25 micromol/L). In terms of microg/mL, the substance was more active (7.6 microg/mL) than this standard antifungal drug (16.6 microg/mL).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / chemistry*
  • 4-Butyrolactone / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry*
  • Antifungal Agents / pharmacology*
  • Chlorobenzenes / chemical synthesis
  • Chlorobenzenes / chemistry*
  • Chlorobenzenes / pharmacology*
  • Cyclization
  • Drug Design
  • Fungi / drug effects*
  • Humans
  • Ketoconazole / pharmacology
  • Molecular Structure

Substances

  • 3-(3,4-dichlorophenyl)-5-methyl-2H,5H-furan-2-one
  • Antifungal Agents
  • Chlorobenzenes
  • incrustoporin
  • 4-Butyrolactone
  • Ketoconazole