N-Sulfonyl homoserine lactones as antagonists of bacterial quorum sensing

A series of 11 N -sulfonyl homoserine lactones has been synthesised. Some of them were found to competitively inhibit the action of 3-oxohexanoyl- L -homoserine lactone, the natural inducer of bioluminescence in the bacterium Vibrio fischeri . Molecular modeling suggests a possible explanation based on the prevention of structural rearrangements necessary for the formation of the active dimer of LuxR. A series of 11 new analogues of N -acylhomoserine lactones in which the carboxamide bond was replaced by a sulfonamide one, has been synthesised. These compounds were evaluated for their ability to competitively inhibit the action of 3-oxohexanoyl- L -homoserine lactone, the natural ligand of the quorum sensing transcriptional regulator LuxR, which in turn activates expression of bioluminescence in the model bacterium Vibrio fischeri . Several compounds were found to display antagonist activity. Molecular modeling suggests that the latter prevent a cascade of structural rearrangements necessary for the formation of the active LuxR dimer.