Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors

Abstract Novel pyrone-derived quorum sensing (QS) ligands to inhibit the binding of OdDHL to the LasR of Pseudomonas aeruginosa were designed, synthesized and evaluated. Among the analogs, the most potent compound 8 exhibited strong in vitro inhibitory activities against biofilm formation and down-regulated OdDHL/LasR-associated genes by 35–67%. The binding mode of 8 in silico was highly similar to that of the crystal ligand OdDHL in the active site of LasR.