Synthesis and evaluation of the quorum sensing inhibitory effect of substituted triazolyldihydrofuranones

Bioorg Med Chem. 2012 Aug 1;20(15):4737-43. doi: 10.1016/j.bmc.2012.06.009. Epub 2012 Jun 9.

Abstract

Acylhomoserine lactone (AHL) analogues in which the amide function is replaced by a triazole group were synthesized and evaluated for their effect on quorum sensing (QS) and biofilm formation in Burkholderia cenocepacia and Pseudomonas aeruginosa. In addition, the influence of the length of the acyl-mimicking chain was investigated. The compounds showed selectivity between two different AHL QS systems. 3-(1H-1,2,3-Triazol-1-yl)dihydrofuran-2(3H)-ones, in which the 4-substituent best resembled the acyl chain of the native AHL molecule exhibited significant QS agonistic and antagonistic activities. Replacing this aliphatic substituent by a phenyl-containing moiety resulted in active inhibitors of QS. The most active compounds showed biofilm inhibitory as well as biofilm eradicating activities in both test organisms.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Burkholderia cenocepacia / drug effects
  • Dose-Response Relationship, Drug
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology*
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects
  • Quorum Sensing / drug effects*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • 3-(1H-1,2,3-triazol-1-yl)dihydrofuran-2(3H)-one
  • Anti-Bacterial Agents
  • Furans
  • Triazoles