当前位置：
X-MOL 学术
›
J. Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Design and Synthesis of 4-Fluorophenyl-5-methylene-2(5H)-furanone Derivatives as Potent Quorum Sensing Inhibitors
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2023-06-13 , DOI: 10.1021/acs.jmedchem.2c01866 Panpan Zhang 1 , Weijin Chen 1 , Yang-Chun Ma 1 , Bingfang Bai 1 , Guanglin Sun 1 , Shenyan Zhang 1 , Xiaohong Chang 1 , Yingmei Wang 1 , Nan Jiang 1 , Xianghui Zhang 1 , Shutao Ma 1
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2023-06-13 , DOI: 10.1021/acs.jmedchem.2c01866 Panpan Zhang 1 , Weijin Chen 1 , Yang-Chun Ma 1 , Bingfang Bai 1 , Guanglin Sun 1 , Shenyan Zhang 1 , Xiaohong Chang 1 , Yingmei Wang 1 , Nan Jiang 1 , Xianghui Zhang 1 , Shutao Ma 1
Affiliation
|
Quorum sensing inhibitors (QSIs) are a class of compounds that can reduce the pathogenicity of bacteria without affecting bacterial growth. In this study, we designed and synthesized four series of 4-fluorophenyl-5-methylene-2(5H)-furanone derivatives and evaluated their QSI activities. Among them, compound 23e not only showed excellent inhibitory activity against various virulence factors but also significantly enhanced the inhibitory activity of antibiotics ciprofloxacin and clarithromycin against two strains of Pseudomonas aeruginosa in vitro. What is even more exciting is that it remarkably increased the antibacterial effect in vivo in combination with ciprofloxacin in the bacteremia model infected with P. aeruginosa PAO1. Moreover, 23e had little hemolytic activity to mouse erythrocytes. Further, the results of GFP reporter fluorescence strain inhibition and β-galactosidase activity inhibition experiments demonstrated that 23e simultaneously targeted the three quorum sensing systems in P. aeruginosa. As a result, compound 23e could be used as an effective QSI for further development against bacterial infections.
中文翻译：
作为有效群体感应抑制剂的 4-氟苯基-5-亚甲基-2(5H)-呋喃酮衍生物的设计与合成
群体感应抑制剂（QSI）是一类可以降低细菌致病性而不影响细菌生长的化合物。在本研究中，我们设计并合成了四个系列的4-氟苯基-5-亚甲基-2(5 H )-呋喃酮衍生物，并评估了它们的QSI活性。其中，化合物23e不仅对多种毒力因子表现出优异的抑制活性，而且在体外显着增强抗生素环丙沙星和克拉霉素对两株铜绿假单胞菌 的抑制活性。更令人兴奋的是，它与环丙沙星联合使用，在感染细菌的菌血症模型中显着增加了体内抗菌效果。铜绿假单胞菌PAO1。此外，23e对小鼠红细胞几乎没有溶血活性。此外，GFP报告荧光菌株抑制和β-半乳糖苷酶活性抑制实验的结果表明，23e同时靶向铜绿假单胞菌中的三个群体感应系统。因此，化合物23e可用作有效的 QSI，进一步开发抗细菌感染的方法。
更新日期：2023-06-13
中文翻译：
作为有效群体感应抑制剂的 4-氟苯基-5-亚甲基-2(5H)-呋喃酮衍生物的设计与合成
群体感应抑制剂（QSI）是一类可以降低细菌致病性而不影响细菌生长的化合物。在本研究中，我们设计并合成了四个系列的4-氟苯基-5-亚甲基-2(5 H )-呋喃酮衍生物，并评估了它们的QSI活性。其中，化合物23e不仅对多种毒力因子表现出优异的抑制活性，而且在体外显着增强抗生素环丙沙星和克拉霉素对两株铜绿假单胞菌 的抑制活性。更令人兴奋的是，它与环丙沙星联合使用，在感染细菌的菌血症模型中显着增加了体内抗菌效果。铜绿假单胞菌PAO1。此外，23e对小鼠红细胞几乎没有溶血活性。此外，GFP报告荧光菌株抑制和β-半乳糖苷酶活性抑制实验的结果表明，23e同时靶向铜绿假单胞菌中的三个群体感应系统。因此，化合物23e可用作有效的 QSI，进一步开发抗细菌感染的方法。
京公网安备 11010802027423号