ArticleJournal of medicinal chemistry2013
Targeting botulinum A cellular toxicity: a prodrug approach.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- An early scoring system to predict mechanical ventilation for botulism: a single-center-based study.World journal of emergency medicine · 2024Article
- Transformation of a Metal Chelate into a "Catch and Anchor" Inhibitor of Botulinum A Protease.International journal of molecular sciences · 2023Article
- Identification of Slow-Binding Inhibitors of the BoNT/A Protease.ACS medicinal chemistry letters · 2022Article
- Irreversible inhibition of BoNT/A protease: proximity-driven reactivity contingent upon a bifunctional approach.RSC medicinal chemistry · 2021Article
- Co-Prodrugs of 7-Ethyl-10-hydroxycamptothecin and Vorinostat with in Vitro Hydrolysis and Anticancer Effects.ACS omega · 2020Article
- Strategies to Counteract Botulinum Neurotoxin A: Nature's Deadliest Biomolecule.Accounts of chemical research · 2019Article
- Enzyme-Activated Fluorogenic Probes for Live-Cell and in Vivo Imaging.ACS chemical biology · 2018Review
- HACS medicinal chemistry letters · 2018Article
- Discovery of a para-Acetoxy-benzyl Ester Prodrug of a Hydroxamate-Based Glutamate Carboxypeptidase II Inhibitor as Oral Therapy for Neuropathic Pain.Journal of medicinal chemistry · 2017Article
- Design, synthesis and evaluation of antiproliferative activity of melanoma-targeted histone deacetylase inhibitors.Bioorganic & medicinal chemistry letters · 2017Article
- Cellular Protection of SNAP-25 against Botulinum Neurotoxin/A: Inhibition of Thioredoxin Reductase through a Suicide Substrate Mechanism.Journal of the American Chemical Society · 2016Article
- Probing BoNT/A protease exosites: implications for inhibitor design and light chain longevity.Biochemistry · 2014Article
- Synthesis/biological evaluation of hydroxamic acids and their prodrugs as inhibitors for Botulinum neurotoxin A light chain.Bioorganic & medicinal chemistry · 2014Article
- A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy.International journal of nanomedicineArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The botulinum neurotoxin light chain (LC) protease has become an important therapeutic target for postexposure treatment of botulism. Hydroxamic acid based small molecules have proven to be potent inhibitors of LC/A with nanomolar Ki values, yet they lack cellular activity conceivably due to low membrane permeability. To overcome this potential liability, we investigated two prodrug strategies, 1,4,2-dioxazole and carbamate, based on our 1-adamantylacetohydroxamic acid scaffold. The 1,4,2-dioxazole prodrug did not demonstrate cellular activity, however, carbamates exhibited cellular potency with the most active compound displaying an EC50 value of 20 μM. Cellular trafficking studies were conducted using a "fluorescently silent" prodrug that remained in this state until cellular uptake was complete, which allowed for visualization of the drug's release inside neuronal cells. In sum, this research sets the stage for future studies leveraging the specific targeting and delivery of these prodrugs, as well as other antibotulinum agents, into neuronal cells.
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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.