Synthesis and Biological Evaluation of Novel L-Homoserine Lactone Analogs as Quorum Sensing Inhibitors of Pseudomonas aeruginosa

Haoyue Liu; Qianhong Gong; Chunying Luo; Yongxi Liang; Xiaoyan Kong; Chunli Wu; Pengxia Feng; Qing Wang; Hui Zhang; M.A. Wireko

doi:10.1248/cpb.c19-00359

Regular Articles

Synthesis and Biological Evaluation of Novel L-Homoserine Lactone Analogs as Quorum Sensing Inhibitors of Pseudomonas aeruginosa

Haoyue Liu, Qianhong Gong, Chunying Luo, Yongxi Liang, Xiaoyan Kong, Chunli Wu , Pengxia Feng, Qing Wang, Hui Zhang, M.A. Wireko

Author information

Haoyue Liu
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation
Qianhong Gong
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China
Chunying Luo
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation
Yongxi Liang
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation
Xiaoyan Kong
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation
Chunli Wu Corresponding author
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation
Pengxia Feng
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation
Qing Wang
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation
Hui Zhang
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation
M.A. Wireko
School of Pharmaceutical Sciences, Zhengzhou University
Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China
Key Laboratory of Henan Province for Drug Quality and Evaluation

Keywords: quorum sensing, L-homoserine lactone, Pseudomonas aeruginosa, dithiocarbamate, phenylurea, benzothiazolyl

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Supplementary material

2019 Volume 67 Issue 10 Pages 1088-1098

DOI https://doi.org/10.1248/cpb.c19-00359

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Abstract

In this study, we synthesized four series of novel L-homoserine lactone analogs and evaluated their in vitro quorum sensing (QS) inhibitory activity against two biomonitor strains, Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PAO1. Studies of the structure–activity relationships of the set of L-homoserine lactone analogs indicated that phenylurea-containing N-dithiocarbamated homoserine lactones are more potent than (Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (C30), a positive control for biofilm formation. In particular, compared with C30, QS inhibitor 11f significantly reduced the production of virulence factors (pyocyanin, elastase and rhamnolipid), swarming motility, the formation of biofilm and the mRNA level of QS-related genes regulated by the QS system of PAO1. These results reveal 11f as a potential lead compound for developing novel antibacterial quorum sensing inhibitors.

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