Abstract
Botulinum neurotoxins are the most toxic proteins currently known. Based on a recently identified potent lead structure, 2,4-dichlorocinnamic acid hydroxamate, herein we report on the structure-activity relationship of a series of hydroxamate BoNT/A inhibitors. Among them, 2-bromo-4-chlorocinnamic acid hydroxamate, 2-methyl-4-chlorocinnamic acid hydroxamate, and 2-trifluoromethyl-4-chlorocinnamic acid hydroxamate displayed comparable inhibitory activity to that of the lead structure.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Botulinum Toxins, Type A / chemical synthesis*
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Botulinum Toxins, Type A / pharmacology*
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / pharmacology*
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Neurotoxins / chemical synthesis
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Neurotoxins / pharmacology
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Peptide Hydrolases / metabolism
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / pharmacology*
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Structure-Activity Relationship
Substances
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Hydroxamic Acids
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Neurotoxins
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Protease Inhibitors
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cinnamoylhydroxamic acid
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Peptide Hydrolases
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Botulinum Toxins, Type A