Design, synthesis and evaluation of halogenated furanone derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa

Eur J Pharm Sci. 2019 Dec 1:140:105058. doi: 10.1016/j.ejps.2019.105058. Epub 2019 Aug 28.

Abstract

The biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) is regulated by a phenomenon of quorum sensing (QS). With 5-hydroxyl-3,4-halogenated-5H-furan-2-ones as beginning, analogs bearing alkyl chains, vinyl bromide, or aromatic rings were designed and synthesized. The minimum inhibitory concentration (MIC) of the compounds against P. aeruginosa was assayed and the biofilm inhibition ratio was determined at different concentrations lower than the MIC. C-5 aromatic substituted furanones showed remarkable biofilm formation as well as inhibition of virulence factor production in P. aeruginosa. Fluorescence report analysis identified the QS regulatory mechanism of the most active compound 29. This study provides us a novel candidate for combating drug resistant bacteria strains by merely inhibiting biofilm formation. Without suppressing the regular life cycle of the bacteria, bacterial resistance mechanisms may not be activated.

Keywords: Biofilm; Furanones; Pseudomonas aeruginosa; Quorum sensing.

MeSH terms

  • Animals
  • Biofilms / drug effects
  • Cell Survival / drug effects
  • Furans / chemistry*
  • Furans / pharmacology*
  • Halogenation
  • Mice
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Quorum Sensing / drug effects*
  • RAW 264.7 Cells
  • Virulence Factors / metabolism

Substances

  • Furans
  • Virulence Factors