Design and Synthesis of 3‑Hydroxy-pyridin-4(1H)‑ones-Ciprofloxacin Conjugates as Dual Antibacterial and Antibiofilm Agents against Pseudomonas aeruginosa
Design and Synthesis of 3‑Hydroxy-pyridin-4(1H)‑ones-Ciprofloxacin Conjugates as Dual Antibacterial and Antibiofilm Agents against Pseudomonas aeruginosa
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3-羟基-吡啶-4(1H)-酮-环丙沙星缀合物作为抗铜绿假单胞菌双重抗菌和抗生物膜剂的设计与合成
DOI：
10.1021/acs.jmedchem.2c02044
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发表时间：
2023
影响因子：
7.3
通讯作者：
Chen Wei-Min
中科院分区：
文献类型：
--
作者：
Wang Yuan-Yuan;Zhang Xiao-Yi;Zhong Xiao-Lin;Huang Yong-Jun;Lin Jing;Chen Wei-Min
铜绿假单胞菌感染通常是复杂的，因为它很容易形成一层生物膜，从而增加对抗生素的耐药性。因此，针对生物膜相关耐药p的新型抗菌药物的开发。急需铜绿杆菌。本文报道了一系列3-羟基吡啶-4(1H)- 1 -环丙沙星偶联物，它们被设计和合成为针对stp的双重抗菌和抗生物膜剂。绿脓杆菌。鉴定出一种潜在的2-取代3-羟基-1,6-二甲基吡啶-4(1H)- 1 -环丙沙星偶联物（5e），对stp的最小抑制浓度分别为0.86 μM和0.43 μM。铜绿菌27853和PAO1，减少78.3%的生物膜形成。此外，5e5还能破坏成熟的生物膜，并杀死融入生物膜的活细菌细胞。对偶联物的抗菌膜机制的研究表明，5e干扰细菌对铁的摄取，抑制细菌的运动，减少毒力的产生。这些结果表明，3-羟基吡啶-4(1H)-环丙沙星偶联物在治疗生物膜相关性耐药方面是有效的。aeruginosainfections。
Pseudomonas aeruginosainfections 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-resistantP. aeruginosais urgently needed. Herein, we report a series of 3-hydroxy-pyridin-4(1H)-ones–ciprofloxacin conjugates that were designed and synthesized as dual antibacterial and antibiofilm agents againstP. aeruginosa. A potential 2-substituted 3-hydroxy-1,6-dimethylpyridin-4(1H)-one–ciprofloxacin conjugate (5e) was identified and had the best minimum inhibitory concentrations of 0.86 and 0.43 μM againstP. aeruginosa27853 and PAO1 and reduced 78.3% of biofilm formation. In addition,5eeradicates mature biofilms and kills living bacterial cells that are incorporated into the biofilm. Studies on the antibiofilm mechanism of conjugates showed that5einterferes with iron uptake by bacteria, inhibits their motility, and reduces the production of virulence. These results demonstrate that 3-hydroxy-pyridin-4(1H)-ones–ciprofloxacin conjugates are potent in the treatment of biofilm-associated drug-resistantP. aeruginosainfections.