Design and Synthesis of 3-Hydroxy-pyridin-4(1)-ones-Ciprofloxacin Conjugates as Dual Antibacterial and Antibiofilm Agents against .

infections are often complicated by the fact that it can easily form a biofilm that increases its resistance to antibiotics. Consequently, the development of novel antibacterial agents against biofilm-associated drug-resistant is urgently needed. Herein, we report a series of 3-hydroxy-pyridin-4(1)-ones-ciprofloxacin conjugates that were designed and synthesized as dual antibacterial and antibiofilm agents against . A potential 2-substituted 3-hydroxy-1,6-dimethylpyridin-4(1)-one-ciprofloxacin conjugate () was identified and had the best minimum inhibitory concentrations of 0.86 and 0.43 μM against 27853 and PAO1 and reduced 78.3% of biofilm formation. In addition, eradicates mature biofilms and kills living bacterial cells that are incorporated into the biofilm. Studies on the antibiofilm mechanism of conjugates showed that interferes with iron uptake by bacteria, inhibits their motility, and reduces the production of virulence. These results demonstrate that 3-hydroxy-pyridin-4(1)-ones-ciprofloxacin conjugates are potent in the treatment of biofilm-associated drug-resistant infections.