3-Hydroxypyridin-4(1)-one Derivatives as Quorum Sensing Inhibitors Attenuate Virulence and Reduce Antibiotic Resistance in .

The development of quorum sensing inhibitors capable of decreasing the production of virulence factors is an effective strategy to overcome resistance in due to the less selective pressure exerted on bacteria. In this study, a series of 3-hydroxypyridin-4(1)-one derivatives bearing a 4-aminomethyl-1,2,3-triazole linker were designed and synthesized as antivirulence agents against . The most potent derivative was identified as a selective inhibitor of the system (IC = 3.7 μM) and its related virulence factor pyocyanin (IC = 2.7 μM). In addition, exhibited moderate biofilm inhibition and significant inhibition of motility phenotypes with low cytotoxicity. Compound showed an obvious antibacterial synergistic effect in combination with antibiotics such as ciprofloxacin and tobramycin in and infection models. Overall, the excellent antivirulence properties of compound make it a potential antibiotic adjuvant for the treatment of infections that may be advanced into preclinical development in the future.