Article

N-Acyl-3-amino-5H-furanone derivatives as new inhibitors of LuxR-dependent quorum sensing: Synthesis, biological evaluation and binding mode study.

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.
Bioorganic & medicinal chemistry letters (impact factor: 2.65). 07/2008; 18(15):4321-4. DOI:10.1016/j.bmcl.2008.06.090
Source: PubMed

ABSTRACT 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.

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Keywords

4-halogeno counterparts
 
conjugated enamide group induces
 
conservatively replaceable residues
 
halogen atom
 
halogenated compounds
 
lactone ring
 
modulate LuxR-dependent bacterial quorum
 
New N-acyl homoserine lactone analogues
 
specific binding modes