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Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors.

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.

SUBMITTER: Capkova K

PROVIDER: S-EPMC2170532 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors.

Capková Katerina K Yoneda Yoshiyuki Y Dickerson Tobin J TJ Janda Kim D KD

Bioorganic & medicinal chemistry letters 20071009 23

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. ...[more]

PMID: 17951059

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