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.
Andromeda-Celeste Gómez  1 ,  Thérèse Lyons  2 ,  Uwe Mamat  3 ,  Daniel Yero  1 ,  Marc Bravo  1 ,  Xavier Daura  4 ,  Osama Elshafee  5 ,  Sascha Brunke  5 ,  Cormac G M Gahan  6 ,  Michelle O'Driscoll  7 ,  Isidre Gibert  8 ,  Timothy P O'Sullivan  9
Affiliations
  • 1. Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • 2. School of Pharmacy, University College Cork, Cork, Ireland.
  • 3. Cellular Microbiology, Research Center Borstel, Leibniz Lung Center, Parkallee 4a, 23845 Borstel, Germany.
  • 4. Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
  • 5. Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Jena, Germany.
  • 6. School of Pharmacy, University College Cork, Cork, Ireland; School of Microbiology, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • 7. School of Pharmacy, University College Cork, Cork, Ireland; School of Chemistry, University College Cork, Cork, Ireland; Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland.
  • 8. Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: [email protected].
  • 9. School of Pharmacy, University College Cork, Cork, Ireland; School of Chemistry, University College Cork, Cork, Ireland; Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland. Electronic address: [email protected].
PMID: 36037789 DOI: 10.1016/j.ejmech.2022.114678
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.
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