N-alkylimidazole derivatives as potential inhibitors of quorum sensing in .

Antimicrobial resistance is a threat to global public health. Microbial resistance is mediated by biofilm formation and virulence behavior during infection. Quorum sensing (QS), a cell-to-cell communication is frequently used by microbes to evade host immune systems. Inhibiting QS channels is a potential route to halt microbial activities and eliminate them. Imidazole has been shown to be a potent warhead in various antimicrobial agents. This study aims to evaluate alkyl-imidazole derivatives as potential inhibitors of QS and to explore the interactions of the compounds with LasR, a key protein in the QS machinery of . The study revealed that imidazole derivatives with longer alkyl chains possessed better antimicrobial activities. Octylimidazole and decylimidazole emerged as compounds with better anti-virulence and biofilm inhibition properties while hexylimidazole showed the best inhibitory activity against PAO1. The binding affinity of the compounds with LasR followed a similar trend as that observed in the QS inhibitory assays, suggesting that interaction with LasR may be important for QS inhibition.