Comparison of seven structurally related coumarins on the inhibition of Quorum sensing of Pseudomonas aeruginosa and Chromobacterium violaceum

Bioorg Chem. 2017 Aug:73:37-42. doi: 10.1016/j.bioorg.2017.05.011. Epub 2017 May 31.

Abstract

Quorum sensing (QS) is a cell-to-cell signaling communication system that controls the virulence behavior of a broad spectrum of bacterial pathogens, participating also in the development of biofilms, responsible of the antibiotic ineffectiveness in many infections. Therefore, QS system is an attractive target for antimicrobial therapy. In this study, we compare the effect of seven structurally related coumarins against bacterial growth, biofilm formation and elastase activity of Pseudomonas aeruginosa. In addition, the anti-pathogenic capacity of the seven coumarins was evaluated on the wild type and the biosensor strain of Chromobacterium violaceum. The comparative study of coumarins showed that molecules with hydroxyl groups on the aromatic ring displayed higher activity on the inhibition of biofilm formation of P. aeruginosa over coumarins with substituents in positions 3 and 4 or without the double 3,4-bond. These 3 or 4-hydroxylated positions caused a decrease in the anti-biofilm activity obtained for coumarin. However, the hydroxyl group in position 3 of the pyrone ring was important for the inhibition of C. violaceum QS and elastolytic activity of P. aeruginosa. The effects observed were active independently of any effect on growth. According to our results, coumarin and its hydroxylated derivatives represent an interesting group of compounds to use as anti-virulence agents against the human pathogen P. aeruginosa.

Keywords: Chromobacterium violaceum; Coumarin; Hydroxycoumarins; Pseudomonas aeruginosa; Quorum sensing.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Chromobacterium / chemistry
  • Chromobacterium / drug effects*
  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Indoles / antagonists & inhibitors
  • Indoles / metabolism
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects*
  • Quorum Sensing / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Coumarins
  • Indoles
  • violacein