期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 31, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2020.115967
关键词
Pseudomonas quinolone system; Quorum sensing inhibitors; Pseudomonas aeruginosa; PqsR antagonist; Dihydropyrrol-2-one (DHP) analogues
资金
- Australian Research Council [DP180100845]
Synthesized novel DHP analogues can serve as quorum sensing inhibitors for treating P. aeruginosa infections, with one compound effectively inhibiting the pqs system. These inhibitors reduce bacterial aggregation and biofilm formation without affecting planktonic growth.
The Pseudomonas quinolone system (pqs) is one of the key quorum sensing systems in antibiotic-resistant P. aeruginosa and is responsible for the production of virulence factors and biofilm formation. Thus, synthetic small molecules that can target the PqsR (MvfR) receptor can be utilized as quorum sensing inhibitors to treat P. aeruginosa infections. In this study, we report the synthesis of novel thioether-linked dihydropyrrol-2-one (DHP) analogues as PqsR antagonists. Compound 7g containing a 2-mercaptopyridyl linkage effectively inhibited the pqs system with an IC50 of 32 mu M in P. aeruginosa PAO1. Additionally, these inhibitors significantly reduced bacterial aggregation and biofilm formation without affecting planktonic growth. The molecular docking study suggest that these inhibitors bind with the ligand binding domain of the MvfR as a competitive antagonist.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据