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新型喹啉 2,8-位衍生物可减弱铜绿假单胞菌的毒力和生物膜形成。

Novel 2, 8-bit derivatives of quinolines attenuate Pseudomonas aeruginosa virulence and biofilm formation.

机构信息

Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.

Pharmacy Department, Qingdao Stomatological Hospital, Qingdao 266000, PR China.

出版信息

Bioorg Med Chem Lett. 2019 Mar 1;29(5):749-754. doi: 10.1016/j.bmcl.2018.12.068. Epub 2019 Jan 3.

Abstract

Signal molecules are stimulators of multiple quroum-sensing virulence and biofilm formation. Small molecule analogues have been suspected as a potent inhibitor in therapeutic strategy. Herein, we synthesized a series of small molecule compounds from the 2, 8-bit derivatives of quinoline by Suzuki coupling reaction. We found that these compounds have the biofilm inhibitory effect in normal condition instead of phosphate limitation state. Furthermore, lacZ reporter strain assay and rhamnolipids as well as pyocyanin experiments showed that these compounds did not affect las and pqs system but reduced the expression of rhl. All these results suggest that quinoline derivatives can be treated as potent inhibitors against biofilm and reduce virulence through the rhl system. This research will be useful in designing new quorum sensing inhibitors to attenuate the infection of bacteria.

摘要

信号分子是多种群体感应毒力和生物膜形成的刺激物。小分子类似物被怀疑是一种有效的治疗策略抑制剂。在这里,我们通过 Suzuki 偶联反应,从喹啉的 2,8-位衍生物合成了一系列小分子化合物。我们发现,这些化合物在正常条件下而不是磷酸盐限制状态下具有生物膜抑制作用。此外,lacZ 报告菌株试验、鼠李糖脂和绿脓菌素实验表明,这些化合物不影响 las 和 pqs 系统,但降低了 rhl 的表达。所有这些结果表明,喹啉衍生物可以作为有效的生物膜抑制剂,通过 rhl 系统降低毒力。这项研究对于设计新的群体感应抑制剂来减轻细菌感染将是有用的。

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