N-Acyl-3-amino-5H-furanone derivatives as new inhibitors of LuxR-dependent quorum sensing: Synthesis, biological evaluation and binding mode study.
New N-acyl homoserine lactone analogues, N-acyl-3-amino-5H-furanone derivatives and some 4-halogeno counterparts, were synthesised and tested for their ability to modulate LuxR-dependent bacterial quorum sensing. Both types of analogues proved to be inhibitors, the halogenated compounds being significantly more active. Molecular modelling suggested that the conjugated enamide group induces two preferential conformations leading to specific binding modes. In addition, the presence of the halogen atom could enhance the fitting of the lactone ring through specific interactions with strictly conserved or conservatively replaceable residues in the LuxR protein family, namely Asp79, Trp94 and Ile81.
Estephane
Jane
J
INSA Lyon, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique, Bât J. Verne, 20 av A. Einstein, 69621 Villeurbanne Cedex, France.
Dauvergne
Julien
J
Soulère
Laurent
L
Reverchon
Sylvie
S
Queneau
Yves
Y
Doutheau
Alain
A
D054742:Acyl-Butyrolactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D048908:Aliivibrio fischeri / Q000502:physiology; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D053038:Quorum Sensing / Q000187:drug effects*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
D054742:Acyl-Butyrolactones; D005663:Furans; D012097:Repressor Proteins; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins