title: 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.
authors.affiliation: Department of Chemistry, and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Katerina
authors.initials: K
authors.lastname: Capková
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yoneda
authors.forename: Tobin J
authors.initials: TJ
authors.lastname: Dickerson
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D019274:Botulinum Toxins, Type A / Q000138:chemical synthesis* / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D009498:Neurotoxins / Q000138:chemical synthesis / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006877:Hydroxamic Acids; D009498:Neurotoxins; D011480:Protease Inhibitors; C030685:cinnamoylhydroxamic acid; D010447:Peptide Hydrolases; D019274:Botulinum Toxins, Type A