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