Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors

Bioorg Med Chem Lett. 2015 Aug 1;25(15):2913-7. doi: 10.1016/j.bmcl.2015.05.054. Epub 2015 May 28.

Abstract

Novel pyrone-derived quorum sensing (QS) ligands to inhibit the binding of OdDHL to the LasR of Pseudomonas aeruginosa were designed, synthesized and evaluated. Among the analogs, the most potent compound 8 exhibited strong in vitro inhibitory activities against biofilm formation and down-regulated OdDHL/LasR-associated genes by 35-67%. The binding mode of 8 in silico was highly similar to that of the crystal ligand OdDHL in the active site of LasR.

Keywords: Biofilm inhibition; Pseudomonas aeruginosa; Pyrone; Quorum sensing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives
  • 4-Butyrolactone / metabolism
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism*
  • Biofilms / drug effects*
  • Homoserine / analogs & derivatives
  • Homoserine / metabolism
  • Humans
  • Molecular Docking Simulation
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / prevention & control
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / physiology
  • Pyrones / chemistry
  • Pyrones / pharmacology*
  • Quorum Sensing / drug effects*
  • Structure-Activity Relationship
  • Trans-Activators / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • LasR protein, Pseudomonas aeruginosa
  • N-(3-oxododecanoyl)homoserine lactone
  • Pyrones
  • Trans-Activators
  • Homoserine
  • 4-Butyrolactone