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

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

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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