Gómez, Andromeda-Celeste; Lyons, Thérèse; Mamat, Uwe; Yero, Daniel; Bravo, Marc; Daura, Xavier; Elshafee, Osama; Brunke, Sascha; Gahan, Cormac G.M.; O’Driscoll, Michelle; Gibert, Isidre; O’Sullivan, Timothy P.

2022

August

European Journal of Medicinal Chemistry

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

Published

WOS: 1 ()

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

242

114678

1-16

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.

1768-3254

10.1016/j.ejmech.2022.114678