ArticleChemMedChem2020
Flexible Fragment Growing Boosts Potency of Quorum-Sensing Inhibitors against Pseudomonas aeruginosa Virulence.
Article in ChemMedChem, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- A quorum sensing antagonist with dual bacterium- and host-directed anti-pathogenic activity againstVirulence · 2026Article
- Quorum sensing inhibition strategies for the control of Pseudomonas aeruginosa infections.World journal of microbiology & biotechnology · 2026Review
- Review
- Inhibitors of the PqsR Quorum-Sensing Receptor Reveal Differential Roles for PqsE and RhlI in Control of Phenazine Production.ACS chemical biology · 2025Article
- Domain adaptable language modeling of chemical compounds identifies potent pathoblockers for Pseudomonas aeruginosa.Communications chemistry · 2025Article
- Cilostazol is a promising anti-pseudomonal virulence drug by disruption of quorum sensing.AMB Express · 2024Article
- Multidimensional Criteria for Virtual Screening of PqsR Inhibitors Based on Pharmacophore, Docking, and Molecular Dynamics.International journal of molecular sciences · 2024Article
- Development of Quinazolinone Derivatives as Modulators of Virulence Factors ofMolecules (Basel, Switzerland) · 2023Article
- Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery.Antibiotics (Basel, Switzerland) · 2023Review
- Towards Translation of PqsR Inverse Agonists: From In Vitro Efficacy Optimization to In Vivo Proof-of-Principle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Insight into the phytochemical profile and antimicrobial activities ofFrontiers in plant science · 2023Article
- Performance upgrade of a microbial explosives' sensor strain by screening a high throughput saturation library of a transcriptional regulator.Computational and structural biotechnology journal · 2023Article
- Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa.Nature communications · 2022Article
- Forces Driving a Magic Bullet to Its Target: Revisiting the Role of Thermodynamics in Drug Design, Development, and Optimization.Life (Basel, Switzerland) · 2022Review
- Anti-Virulence Activity of 3,3'-Diindolylmethane (DIM): A Bioactive Cruciferous Phytochemical with Accelerated Wound Healing Benefits.Pharmaceutics · 2022Article
- Drug Repurposing TargetingAntibiotics (Basel, Switzerland) · 2022Article
- Fragment-to-Lead Medicinal Chemistry Publications in 2020.Journal of medicinal chemistry · 2022Review
- Quorum Sensing Inhibitors to QuenchPharmaceuticals (Basel, Switzerland) · 2021Review
- A New PqsR Inverse Agonist Potentiates Tobramycin Efficacy to Eradicate Pseudomonas aeruginosa Biofilms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Towards the sustainable discovery and development of new antibiotics.Nature reviews. Chemistry · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hit-to-lead optimization is a critical phase in drug discovery. Herein, we report on the fragment-based discovery and optimization of 2-aminopyridine derivatives as a novel lead-like structure for the treatment of the dangerous opportunistic pathogen Pseudomonas aeruginosa. We pursue an innovative treatment strategy by interfering with the Pseudomonas quinolone signal (PQS) quorum sensing (QS) system leading to an abolishment of bacterial pathogenicity. Our compounds act on the PQS receptor (PqsR), a key transcription factor controlling the expression of various pathogenicity determinants. In this target-driven approach, we made use of biophysical screening via surface plasmon resonance (SPR) followed by isothermal titration calorimetry (ITC)-enabled enthalpic efficiency (EE) evaluation. Hit optimization then involved growth vector identification and exploitation. Astonishingly, the latter was successfully achieved by introducing flexible linkers rather than rigid motifs leading to a boost in activity on the target receptor and anti-virulence potency.
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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.