ArticleJournal of medicinal chemistry2012
Lead optimization studies on FimH antagonists: discovery of potent and orally bioavailable ortho-substituted biphenyl mannosides.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 124 citations in OpenAlex.
- Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance.Molecules (Basel, Switzerland) · 2025Article
- Review
- Facile Synthesis of FimH Antagonist and Its Analogues: Simple Entry to ComplexACS medicinal chemistry letters · 2024Article
- Article
- Does size matter? - Comparing pyranoses with septanoses as ligands of the bacterial lectin FimH.European journal of medicinal chemistry · 2024Article
- Discovery of Orally Bioavailable FmlH Lectin Antagonists as Treatment for Urinary Tract Infections.Journal of medicinal chemistry · 2024Article
- Fimbria targeting superparamagnetic iron oxide nanoparticles enhance the antimicrobial and antibiofilm activity of ciprofloxacin against quinolone-resistant E. coli.Microbial biotechnology · 2023Article
- Identifying FmlH lectin-binding small molecules for the prevention of Escherichia coli-induced urinary tract infections using hybrid fragment-based design and molecular docking.Computers in biology and medicine · 2023Article
- Glycomimetics for the inhibition and modulation of lectins.Chemical Society reviews · 2023Review
- Effect of bovine lactoferrin on recurrent urinary tract infections: in vitro and in vivo evidences.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Article
- Emerging Non-Antibiotic Options Targeting Uropathogenic Mechanisms for Recurrent Uncomplicated Urinary Tract Infection.International journal of molecular sciences · 2023Review
- Insightful Improvement in the Design of Potent UropathogenicPharmaceutics · 2023Article
- Article
- Developments in Mannose-Based Treatments for Uropathogenic Escherichia coli-Induced Urinary Tract Infections.Chembiochem : a European journal of chemical biology · 2021Review
- A host receptor enables type 1 pilus-mediated pathogenesis of Escherichia coli pyelonephritis.PLoS pathogens · 2021Article
- FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens.Antibiotics (Basel, Switzerland) · 2020Review
- Interaction with the host: the role of fibronectin and extracellular matrix proteins in the adhesion of Gram-negative bacteria.Medical microbiology and immunology · 2020Review
- Aerobic Catalyzed Oxidative Cross-Coupling ofOrganic letters · 2020Article
- Improving the Switching Capacity of Glyco-Self-Assembled Monolayers on Au(111).Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Reciprocal Cooperation of Type A Procyanidin and Nitrofurantoin Against Multi-Drug Resistant (MDR) UPEC: A pH-Dependent Study.Frontiers in cellular and infection microbiology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Herein, we describe the X-ray structure-based design and optimization of biaryl mannoside FimH inhibitors. Diverse modifications to the biaryl ring to improve druglike physical and pharmacokinetic properties of mannosides were assessed for FimH binding affinity based on their effects on hemagglutination and biofilm formation along with direct FimH binding assays. Substitution on the mannoside phenyl ring ortho to the glycosidic bond results in large potency enhancements several-fold higher than those of corresponding unsubstituted matched pairs and can be rationalized from increased hydrophobic interactions with the FimH hydrophobic ridge (Ile13) or "tyrosine gate" (Tyr137 and Tyr48) also lined by Ile52. The lead mannosides have increased metabolic stability and oral bioavailability as determined from in vitro PAMPA predictive model of cellular permeability and in vivo pharmacokinetic studies in mice, thereby representing advanced preclinical candidates with promising potential as novel therapeutics for the clinical treatment and prevention of recurring urinary tract infections.
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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.