Sep 11, 2008

Small molecules for interference with cell-cell-communication systems in Gram-negative bacteria

Current Medicinal Chemistry
Joost C A JanssensJos Vanderleyden

Abstract

Quorum sensing (QS) systems are bacterial cell-to-cell communication systems that use small molecules as signals. Since QS is involved in the regulation of virulence and biofilm formation in several pathogenic bacteria, it has been suggested as a new target for the development of novel antibacterial therapies. As such, interference with the signal receptors by using chemical compounds has been proposed as an alternative strategy for treatment of bacterial infections and has already shown promising results in combination with traditional antibiotic treatments. In Gram-negative bacteria, the best studied QS systems use N-acyl homoserine lactones (AHLs) as signal molecules. This review provides an overview of all new chemical structure types that inhibit AHL-mediated QS systems as reported during the last three years in scientific journals and in the patent literature. The compounds were classified into three main groups depending on their structure: AHL analogues, 2(5H)-furanones, and compounds that are not structurally related to AHLs. We discuss the biological assays used and the different strategies applied to discover these molecules, including new approaches such as molecular docking for in silico identification of lead stru...Continue Reading

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Mentioned in this Paper

Molecular Stereochemistry
Bacterial cell
Bacteriocidal Agents
Pathogenic Organism
Structure-Activity Relationship
Anterior Horizontal Limb of Lateral Sulcus (Human Only)
Cell Communication
Docking -molecular Interaction
Gram-Negative Bacteria
Virulence

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