Synthesis and evaluation of novel furanones as biofilm inhibitors in opportunistic human pathogens
Gómez Camacho, Andromeda Celeste (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Lyons, Thérèse (University College Cork. School of Pharmacy)
Mamat, Uwe (Leibniz Lung Center. Cellular Microbiology)
Yero, Daniel (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Bravo, Marc (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Daura i Ribera, Xavier (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Elshafee, Osama (Leibniz Institute for Natural Product Research and Infection Biology. Department of Microbial Pathogenicity Mechanisms)
Brunke, Sascha (Leibniz Institute for Natural Product Research and Infection Biology. Department of Microbial Pathogenicity Mechanisms)
Gahan, Cormac G.M. (University College Cork. APC Microbiome Ireland)
O'Driscoll, Michelle (University College Cork. Analytical and Biological Chemistry Research Facility)
Gibert, Isidre (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
O'Sullivan, Timothy P. (University College Cork. Analytical and Biological Chemistry Research Facility)

Data:	2022
Resum:	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.
Ajuts:	Agencia Estatal de Investigación PID2019-111364RB-I00
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Furanones ; Biofilms ; Quorum sensing ; Salmonella enterica ; Staphylococcus aureus ; Pseudomonas aeruginosa ; Escherichia coli ; Stenotrophomonas maltophilia ; Candida albicans
Publicat a:	European Journal of Medicinal Chemistry, Vol. 242 (November 2022) , art. 114678, ISSN 1768-3254

DOI: 10.1016/j.ejmech.2022.114678
PMID: 36037789

16 p, 7.0 MB

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