Benzoquinones as inhibitors of botulinum neurotoxin serotype A
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چکیده
منابع مشابه
Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A.
An in silico screen of the NIH Molecular Library Small Molecule Repository (MLSMR) of ∼350000 compounds and confirmatory bioassays led to identification of chaetochromin A (1) as an inhibitor of botulinum neurotoxin serotype A (BoNT A). Subsequent acquisition and testing of analogues of 1 uncovered two compounds, talaroderxines A (2) and B (3), with improved activity. These are the first fungal...
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Botulinum neurotoxin serotype A (BoNTA) is one of the most toxic substances known. Currently, there is no antidote to BoNTA. Small molecules identified from high-throughput screening reportedly inhibit the endopeptidase--the zinc-bound, catalytic domain of BoNTA--at a drug concentration of 20 microM. However, optimization of these inhibitors is hampered by challenges including the computational...
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TO THE EDITOR—I write in reference to the publication of the articles and commentaries regarding the purported new botulinum neurotoxin serotype H [1–4]. For the past 30 years, the genetics and physiology of Clostridium botulinum, particularly the properties of serotypes and subtypes of botulinum neurotoxins, have been studied in my tier 1 select agent laboratory. I also have a dual use researc...
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An integrated strategy that combined in silico screening and tiered biochemical assays (enzymatic, in vitro, and ex vivo) was used to identify and characterize effective small-molecule inhibitors of Clostridium botulinum neurotoxin serotype A (BoNT/A). Virtual screening was initially performed by computationally docking compounds of the National Cancer Institute (NCI) database into the active s...
متن کاملPost-Intoxication Inhibition of Botulinum Neurotoxin Serotype A within Neurons by Small-Molecule, Non-Peptidic Inhibitors
Botulinum neurotoxins (BoNTs) comprise seven distinct serotypes that inhibit the release of neurotransmitter across neuromuscular junctions, resulting in potentially fatal flaccid paralysis. BoNT serotype A (BoNT/A), which targets synaptosomal-associated protein of 25kDa (SNAP-25), is particularly long-lived within neurons and requires a longer time for recovery of neuromuscular function. There...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry
سال: 2014
ISSN: 0968-0896
DOI: 10.1016/j.bmc.2014.06.004