AHL-dependent quorum sensing inhibition: synthesis and biological evaluation of α-(N-alkyl-carboxamide)-γ-butyrolactones and α-(N-alkyl-sulfonamide)-γ-butyrolactones

Mohamed Boukraa; Mohamad Sabbah; Laurent Soulère; Mohamed L El Efrit; Yves Queneau; Alain Doutheau

doi:10.1016/j.bmcl.2011.09.010

AHL-dependent quorum sensing inhibition: synthesis and biological evaluation of α-(N-alkyl-carboxamide)-γ-butyrolactones and α-(N-alkyl-sulfonamide)-γ-butyrolactones

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6876-9. doi: 10.1016/j.bmcl.2011.09.010. Epub 2011 Sep 10.

Authors

Mohamed Boukraa¹, Mohamad Sabbah, Laurent Soulère, Mohamed L El Efrit, Yves Queneau, Alain Doutheau

Affiliation

¹ INSA Lyon, ICBMS, Bât J. Verne, 20 av A. Einstein, 69621 Villeurbanne Cedex, France.

PMID: 21974956
DOI: 10.1016/j.bmcl.2011.09.010

Abstract

New N-acylhomoserine lactone (AHL) analogues in which the amide function is replaced by a reverse-amide one have been studied as AHL QS modulators. The series of compounds consists of α-(N-alkyl-carboxamide)-γ-butyrolactones, α-(N-alkyl-sulfonamide)-γ-butyrolactones, and 2-(N-alkyl-carboxamide)-cyclopentanones and cyclopentanols. Most active compounds exhibited antagonist activities against LuxR reaching the 30 μM range.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

4-Butyrolactone / analogs & derivatives*
4-Butyrolactone / pharmacology*
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Bacteria / drug effects
Bacterial Infections / drug therapy
Humans
Models, Molecular
Quorum Sensing / drug effects*
Repressor Proteins / antagonists & inhibitors*
Repressor Proteins / metabolism
Trans-Activators / antagonists & inhibitors*
Trans-Activators / metabolism

Substances

Anti-Bacterial Agents
Repressor Proteins
Trans-Activators
LuxR autoinducer binding proteins
4-Butyrolactone