ArticleACS chemical biology2016
Designed Small-Molecule Inhibitors of the Anthranilyl-CoA Synthetase PqsA Block Quinolone Biosynthesis in Pseudomonas aeruginosa.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- Quorum sensing inhibition strategies for the control of Pseudomonas aeruginosa infections.World journal of microbiology & biotechnology · 2026Review
- The Quantification of Drug Accumulation within Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- Vistas in the domain of 3-acetyl-4-hydroxy-2-quinolinone derivatives (AHQ) and their applications.RSC advances · 2025Review
- A Systematic Hierarchical Virtual Screening Model for RhlR Inhibitors Based on PCA, Pharmacophore, Docking, and Molecular Dynamics.International journal of molecular sciences · 2024Article
- Unveiling the hidden language of bacteria: anti-quorum sensing strategies for gram-negative bacteria infection control.Archives of microbiology · 2024Review
- Article
- Synthesis and Biological Evaluation of New Quinoline and Anthranilic Acid Derivatives as Potential Quorum Sensing Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- A Small-Molecule Inhibitor of the Anthranilyl-CoA Synthetase PqsA for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa.Microbiology spectrum · 2022Article
- Inhibitory Effects of Compounds from Plumula nelumbinis on Biofilm and Quorum Sensing Against P. aeruginosa.Current microbiology · 2022Article
- Protein-protein interface analysis of the non-ribosomal peptide synthetase peptidyl carrier protein and enzymatic domains.Synthetic and systems biotechnology · 2022Review
- Quorum Sensing Inhibitors to QuenchPharmaceuticals (Basel, Switzerland) · 2021Review
- Quinolone Signals Related toFrontiers in microbiology · 2021Article
- Bacterial Alkyl-4-quinolones: Discovery, Structural Diversity and Biological Properties.Molecules (Basel, Switzerland) · 2020Review
- Design, Synthesis and Biological Evaluation of Novel Anthraniloyl-AMP Mimics as PQS Biosynthesis Inhibitors AgainstMolecules (Basel, Switzerland) · 2020Article
- Dynamic visualization of type II peptidyl carrier protein recognition in pyoluteorin biosynthesis.RSC chemical biology · 2020Article
- Rational Drug Design forFrontiers in molecular biosciences · 2020Article
- Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors.The Journal of antibiotics · 2019Review
- Quorum Sensing as Antivirulence Target in Cystic Fibrosis Pathogens.International journal of molecular sciences · 2019Review
- Article
- Recent Advances in Anti-virulence Therapeutic Strategies With a Focus on Dismantling Bacterial Membrane Microdomains, Toxin Neutralization, Quorum-Sensing Interference and Biofilm Inhibition.Frontiers in cellular and infection microbiology · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
The Gram-negative bacterial pathogen Pseudomonas aeruginosa uses three interconnected intercellular signaling systems regulated by the transcription factors LasR, RhlR, and MvfR (PqsR), which mediate bacterial cell-cell communication via small-molecule natural products and control the production of a variety of virulence factors. The MvfR system is activated by and controls the biosynthesis of the quinolone quorum sensing factors HHQ and PQS. A key step in the biosynthesis of these quinolones is catalyzed by the anthranilyl-CoA synthetase PqsA. To develop inhibitors of PqsA as novel potential antivirulence antibiotics, we report herein the design and synthesis of sulfonyladeonsine-based mimics of the anthranilyl-AMP reaction intermediate that is bound tightly by PqsA. Biochemical, microbiological, and pharmacological studies identified two potent PqsA inhibitors, anthranilyl-AMS (1) and anthranilyl-AMSN (2), that decreased HHQ and PQS production in P. aeruginosa strain PA14. However, these compounds did not inhibit production of the virulence factor pyocyanin. Moreover, they exhibited limited bacterial penetration in compound accumulation studies. This work provides the most potent PqsA inhibitors reported to date and sets the stage for future efforts to develop analogues with improved cellular activity to investigate further the complex relationships between quinolone biosynthesis and virulence factor production in P. aeruginosa and the therapeutic potential of targeting PqsA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.