Developing Gingerol-Based\nAnalogs against Pseudomonas aeruginosa Infections

Pseudomonas aeruginosa (P. aeruginosa), a Gram-negative\nopportunistic pathogen,\nproduces virulent factors and forms biofilms through a quorum sensing\n(QS) mechanism. Modulating QS networks is considered an effective\nstrategy for treating P. aeruginosa infections. Particularly, the <i>rhl</i> system, one of\nthe QS networks, can be a potential target in treating patients with\nchronic infections. We previously discovered that gingerol acts as\na RhlR antagonist of P. aeruginosa.\nBased on the chemical structure of gingerol, we have designed and\nsynthesized gingerol derivatives by introducing various functional\ngroups in the middle and tail regions. A comprehensive structure–activity\nrelationship study showed that compound <b>5a</b> substituted\nwith phenyl group in the tail region was the most potent in various\nbiological assessments, such as RhlR binding affinity, <i>rhl</i> gene expression, and virulence factor production of P. aeruginosa. Furthermore, compound <b>5a</b> decreased the biofilm formation and pathogenicity of P. aeruginosa. Interestingly, compound <b>5a</b> also influenced <i>las</i> system in addition to the <i>rhl</i> system. Taken together, compound <b>5a</b> can\nbe utilized as a potent compound for controlling P.\naeruginosa infection.