Synthetic homoserine lactone-derived sulfonylureas as inhibitors of Vibrio fischeri quorum sensing regulator

A series of 9 homoserine lactone-derived sulfonylureas, were prepared and found to inhibit the acyl-homoserine lactones-dependent Vibrio fischeri quorum sensing regulator. Molecular modelling suggested that the inhibitory activity could be related to the perturbation of the hydrogen-bond network in the ligand–protein complexes. A series of 9 homoserine lactone-derived sulfonylureas substituted by an alkyl chain, some of them bearing a phenyl group at the extremity, have been prepared. All compounds were found to inhibit the action of 3-oxo-hexanoyl- l-homoserine lactone, the natural inducer of bioluminescence in the bacterium Vibrio fischeri, the aliphatic compounds being more active than their phenyl-substituted counterparts. Molecular modelling studies performed on the most active compound in each series suggest that the antagonist activity could be related to the perturbation of the hydrogen-bond network in the ligand–protein complexes.