Botulinum neurotoxin serotype A inhibitors: small-molecule mercaptoacetamide analogs.
Botulinum neurotoxin elicits its paralytic activity through a zinc-dependant metalloprotease that cleaves proteins involved in neurotransmitter release. Currently, no drugs are available to reverse the effects of botulinum intoxication. Herein we report the design of a novel series of mercaptoacetamide small-molecule inhibitors active against botulinum neurotoxin serotype A. These analogs show low micromolar inhibitory activity against the isolated enzyme. Structure-activity relationship studies for a series of mercaptoacetamide analogs of 5-amino-3-phenylpyrazole reveal components essential for potent inhibitory activity.
Moe
Scott T
ST
Absolute Science, Inc., Lexington, MA 02421, United States.
Thompson
Andrew B
AB
Smith
Genessa M
GM
Fredenburg
Ross A
RA
Stein
Ross L
RL
Jacobson
Alan R
AR