ArticleACS infectious diseases2024
Investigations of Thiosemicarbazides as Botulinum Toxin Active-Site Inhibitors: Enzyme, Cellular, and Rodent Intoxication Studies.
Article in ACS infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed.
- Bifunctional Inhibition of Botulinum Neurotoxin A Protease: Unexpected Active Site Inhibition Enhances Covalent Targeting of an Allosteric Site.Journal of medicinal chemistry · 2025Article
- Novel Copper(II) Coordination Compounds Containing Pyridine Derivatives ofMolecules (Basel, Switzerland) · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Botulinum neurotoxin type A (BoNT/A) is an exceptionally potent neurotoxin of great therapeutic value; however, it is also considered a weapon of mass destruction, as it is one of the most poisonous biological substances known to man. The etiology behind BoNT/A is its action as a zinc-dependent protease, which can cause extended paralysis through the cleavage of SNARE proteins. Thiosemicarbazones, known zinc chelators, provide a privileged scaffold that can be leveraged for the development of BoNT/A LC inhibitors. Through a combination of biochemical and kinetic assays, it was demonstrated that the thiosemicarbazone ZMC1, an antitumor agent, is an effective competitive inhibitor of the BoNT/A LC. Based on these results, a series of thiosemicarbazones were designed/synthesized using structure-based analysis and examined in enzyme activity and cell-based assays. From this screen, two analogues presented noteworthy cellular activity. The most potent inhibitors were then tested in a BoNT/A mouse lethality assay, providing statistically significant prolonged survival.
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