Bicyclic brominated furanones: A new class of quorum sensing modulators that inhibit bacterial biofilm formation

Sijie Yang, Osama A. Abdel-Razek, Fei Cheng, Debjyoti Bandyopadhyay, Gauri S. Shetye, Guirong Wang, Yan Yeung Luk

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Both natural and synthetic brominated furanones are known to inhibit biofilm formation by bacteria, but their toxicity to mammalian cells is often not reported. Here, we designed and synthesized a new class of brominated furanones (BBFs) that contained a bicyclic structure having one bromide group with well-defined regiochemistry. This class of molecules exhibited reduction in the toxicity to mammalian cells (human neuroblastoma SK-N-SH) and did not inhibit bacteria (Pseudomonas aeruginosa and Escherichia coli) growth, but retained the inhibitory activity towards biofilm formation of bacteria. In addition, all the BBFs inhibited the production of virulence factor elastase B in P. aeruginosa. To explore the effect of BBFs on quorum sensing, we used a reporter gene assay and found that 6-BBF and 7-BBF exhibited antagonistic activities for LasR protein in the lasI quorum sensing circuit, while 5-BBF showed agonistic activity for the rhlI quorum sensing circuit. This study suggests that structural variation of brominated furanones can be designed for targeted functions to control biofilm formation.

Original languageEnglish (US)
Pages (from-to)1313-1317
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number4
DOIs
StatePublished - Feb 15 2014

Keywords

  • Biofilm inhibition
  • Cell signaling
  • Furanones
  • Toxicity
  • Virulence factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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