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新型香豆素衍生物通过抑制群体感应系统和铁稳态作为抗菌增效剂对抗 。

Novel Coumarin Derivatives Inhibit the Quorum Sensing System and Iron Homeostasis as Antibacterial Synergists against .

机构信息

Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P. R. China.

College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P. R. China.

出版信息

J Med Chem. 2023 Nov 9;66(21):14735-14754. doi: 10.1021/acs.jmedchem.3c01268. Epub 2023 Oct 24.

Abstract

() is well-known to cause biofilm-associated drug resistance and infections that often lead to treatment failure. Herein, we reported a dual-acting antibiofilm strategy by inhibiting both the bacterial quorum sensing system and the iron uptake system. A series of coumarin derivatives were synthesized and evaluated, and compound was identified as the most effective biofilm inhibitor (IC = 3.6 μM). Further mechanistic studies have confirmed that not only inhibits the QS systems but also competes strongly with pyoverdine as an iron chelator, causing an iron deficiency in . Additionally, significantly improved the synergistic antibacterial effects of ciprofloxacin and tobramycin by more than 200-1000-fold compared to the single-dose antibiotic treatments. Therefore, our study has shown that is a potentially novel antibacterial synergist candidate to treat bacterial infections.

摘要

()众所周知会导致生物膜相关的耐药性和感染,这往往导致治疗失败。在此,我们报告了一种双重作用的抗生物膜策略,通过抑制细菌群体感应系统和铁摄取系统。合成并评价了一系列香豆素衍生物,化合物 被鉴定为最有效的生物膜抑制剂(IC=3.6 μM)。进一步的机制研究证实,不仅抑制了 QS 系统,而且还强烈地与绿脓菌素竞争作为铁螯合剂,导致 中的铁缺乏。此外,与单剂量抗生素治疗相比,显著提高了环丙沙星和妥布霉素的协同抗菌作用超过 200-1000 倍。因此,我们的研究表明,是一种有潜力的新型抗菌增效剂候选物,可用于治疗细菌感染。

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