Synthesis and evaluation of novel furanones as biofilm inhibitors in opportunistic human pathogens

Eur J Med Chem. 2022 Nov 15:242:114678. doi: 10.1016/j.ejmech.2022.114678. Epub 2022 Aug 20.

Abstract

Diseases caused by biofilm-forming pathogens are becoming increasingly prevalent and represent a major threat to human health. This trend has prompted a search for novel inhibitors of microbial biofilms which could, for example, be used to potentiate existing antibiotics. Naturally-occurring, halogenated furanones isolated from marine algae have proven to be effective biofilm inhibitors in several bacterial species. In this work, we report the synthesis of a library of novel furanones and their subsequent evaluation as biofilm inhibitors in several opportunistic human pathogens including S. enterica, S. aureus, E. coli, S. maltophilia, P. aeruginosa and C. albicans. A number of the most potent compounds were subjected to further analysis by confocal laser-scanning microscopy for their effects on P. aeruginosa and C. albicans biofilms individually, in addition to mixed polymicrobial biofilms. Lastly, we investigated the impact of a promising candidate on survival rates in vivo using a Galleria mellonella model.

Keywords: Biofilms; Candida albicans; Escherichia coli; Furanones; Pseudomonas aeruginosa; Quorum sensing; Salmonella enterica; Staphylococcus aureus; Stenotrophomonas maltophilia.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Biofilms
  • Candida albicans
  • Escherichia coli*
  • Humans
  • Pseudomonas aeruginosa
  • Staphylococcus aureus*

Substances

  • Anti-Bacterial Agents