Structure-activity relationship of brominated 3-alkyl-5-methylene-2(5H)-furanones and alkylmaleic anhydrides as inhibitors of Salmonella biofilm formation and quorum sensing regulated bioluminescence in Vibrio harveyi.
A library of 25 1'-unsubstituted and 1'-bromo or 1'-acetoxy 3-alkyl-5-methylene-2(5H)-furanones and two 3-alkylmaleic anhydrides was synthesized using existing and new methods. This library was tested for the antagonistic effect against the biofilm formation by Salmonella Typhimurium and the quorum sensing regulated bioluminescence of Vibrio harveyi. The length of the 3-alkyl chain and the bromination pattern of the ring structure were found to have a major effect on the biological activity of the 1'-unsubstituted furanones. Remarkably, the introduction of a bromine atom on the 1' position of the 3-alkyl chain did drastically enhance the activity of the furanones in both biological test systems. The introduction of an acetoxy function in this position did in general not improve the activity. Finally, the potential of the (bromo)alkylmaleic anhydrides as a new and chemically easily accessible class of biofilm and quorum sensing inhibitors was demonstrated.
Steenackers
Hans P
HP
Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, B-3001 Leuven, Belgium.
Levin
Jeremy
J
Janssens
Joost C
JC
De Weerdt
Ami
A
Balzarini
Jan
J
Vanderleyden
Jos
J
De Vos
Dirk E
DE
De Keersmaecker
Sigrid C
SC
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D054879:Halogenation; D049449:Luminescence; D008299:Maleic Anhydrides / Q000737:chemistry / Q000494:pharmacology*; D053038:Quorum Sensing / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D014733:Vibrio / Q000187:drug effects* / Q000502:physiology
D000900:Anti-Bacterial Agents; D005663:Furans; D008299:Maleic Anhydrides