PUBLICATION
New Pqs Quorum Sensing System Inhibitor as an Antibacterial Synergist against Multidrug-Resistant Pseudomonas aeruginosa
- Authors
- Liu, J., Hou, J.S., Chang, Y.Q., Peng, L.J., Zhang, X.Y., Miao, Z.Y., Sun, P.H., Lin, J., Chen, W.M.
- ID
- ZDB-PUB-220208-1
- Date
- 2022
- Source
- Journal of medicinal chemistry 65: 688-709 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/pharmacology*
- Biofilms/drug effects
- Cell Line
- Cell Survival/drug effects
- Colony Count, Microbial
- Drug Resistance, Multiple, Bacterial/drug effects*
- Drug Synergism
- Microbial Sensitivity Tests
- Pseudomonas Infections/microbiology
- Pseudomonas aeruginosa/drug effects*
- Pyocyanine/antagonists & inhibitors
- Pyridines/chemical synthesis
- Pyridines/pharmacology
- Quinolones/metabolism
- Quorum Sensing/drug effects*
- Zebrafish
- PubMed
- 34951310 Full text @ J. Med. Chem.
Citation
Liu, J., Hou, J.S., Chang, Y.Q., Peng, L.J., Zhang, X.Y., Miao, Z.Y., Sun, P.H., Lin, J., Chen, W.M. (2022) New Pqs Quorum Sensing System Inhibitor as an Antibacterial Synergist against Multidrug-Resistant Pseudomonas aeruginosa. Journal of medicinal chemistry. 65:688-709.
Abstract
Development of new bacterial biofilm inhibitors as antibacterial synergists is an effective strategy to solve the resistance of Pseudomonas aeruginosa. In this paper, a series of 3-hydroxy-pyridin-4(1H)-ones were synthesized and evaluated, and the hit compound (20p) was identified with the effects of inhibiting the production of pyocyanin (IC50 = 8.6 μM) and biofilm formation (IC50 = 4.5 μM). Mechanistic studies confirmed that 20p inhibits the formation of bacterial biofilm by inhibiting the expression of pqsA, blocking pqs quorum sensing system quinolone biosynthesis. Moreover, we systematically investigated the bactericidal effects of combining currently approved antibiotics for CF including tobramycin, ciprofloxacin, and colistin E with 20p, which showed obvious antibacterial synergy to overcome antibiotics resistance in multidrug-resistant P. aeruginosa biofilms. The result indicates that compound 20p may be used in the future as a potentially novel antibacterial synergist candidate for the treatment of P. aeruginosa infections.
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Orthology
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Mapping