ArticleJournal of medicinal chemistry2014
Identification of clinically viable quinolinol inhibitors of botulinum neurotoxin A light chain.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Efficacy of botulinum toxin type A for spasticity management and motor function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials.Frontiers in neurologyPooled it
- Development of novel 2-[(8-hydroxyquinolin-7-yl)(phenyl)methylamino]benzoic acid derivatives for inhibiting the catalytic activity of botulinum neurotoxins type B and F: in silico, in vitro & in vivo evaluation.Archives of toxicology · 2026Article
- Botulinum neurotoxin: from molecular pathogenesis to emerging countermeasures.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Therapeutic potential of [(8-hydroxyquinolin-7-yl)(phenyl)methylamino] benzoic acid regioisomers against human-intoxicating botulinum neurotoxin serotypes: computational modeling to in vivo protection.Journal of computer-aided molecular design · 2026Article
- A Superior Corrosion Protection of Mg Alloy via Smart Nontoxic Hybrid Inhibitor-Containing Coatings.Molecules (Basel, Switzerland) · 2023Article
- Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery.Antibiotics (Basel, Switzerland) · 2023Review
- Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update.Archives of toxicology · 2022Review
- Identification of Slow-Binding Inhibitors of the BoNT/A Protease.ACS medicinal chemistry letters · 2022Article
- Botulinum toxin as an ultrasensitive reporter for bacterial and SARS-CoV-2 nucleic acid diagnostics.Biosensors & bioelectronics · 2021Article
- Drug screening to identify compounds to act as co-therapies for the treatment of Burkholderia species.PloS one · 2021Article
- Identification of 3-hydroxy-1,2-dimethylpyridine-4(1RSC medicinal chemistry · 2021Article
- An 8-Hydroxy-Quinoline Derivative Protects Against Lipopolysaccharide-Induced Lethality in Endotoxemia by Inhibiting HMGB1-Mediated Caspase-11 Signaling.Frontiers in pharmacology · 2021Article
- Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A.Journal of medicinal chemistry · 2020Article
- Protein-Catalyzed Capture Agents.Chemical reviews · 2019Review
- Strategies to Counteract Botulinum Neurotoxin A: Nature's Deadliest Biomolecule.Accounts of chemical research · 2019Article
- Targeting Metalloenzymes for Therapeutic Intervention.Chemical reviews · 2019Review
- Natural Compounds and Their Analogues as Potent Antidotes against the Most Poisonous Bacterial Toxin.Applied and environmental microbiology · 2018Article
- Metal Ions Effectively Ablate the Action of Botulinum Neurotoxin A.Journal of the American Chemical Society · 2017Article
- Newly Designed Quinolinol Inhibitors Mitigate the Effects of Botulinum Neurotoxin A in Enzymatic, Cell-Based, and ex Vivo Assays.Journal of medicinal chemistry · 2017Article
- Picolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain.Chemical communications (Cambridge, England) · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Botulinum neurotoxins (BoNT) are the most potent toxins known and a significant bioterrorist threat. Few small molecule compounds have been identified that are active in cell-based or animal models, potentially due to toxin enzyme plasticity. Here we screened commercially available quinolinols, as well as synthesized hydroxyquinolines. Seventy-two compounds had IC50 values below 10 μM, with the best compound exhibiting submicromolar inhibition (IC50 = 0.8 μM). Structure-activity relationship trends showed that the enzyme tolerates various substitutions at R1 but has a clear preference for bulky aryl amide groups at R2, while methylation at R3 increased inhibitor potency. Evaluation of the most potent compounds in an ADME panel showed that these compounds possess poor solubility at pH 6.8, but display excellent solubility at low pH, suggesting that oral dosing may be possible. Our data show the potential of quinolinol compounds as BoNT therapeutics due to their good in vitro potencies and favorable ADME properties.
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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.