Design of a potent reactivator of tabun-inhibited acetylcholinesterase--synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203)
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
G0400930
Medical Research Council - United Kingdom
PubMed
17924614
DOI
10.1021/jm070653r
Knihovny.cz E-resources
- MeSH
- Acetylcholinesterase chemistry MeSH
- Chemical Warfare Agents chemistry MeSH
- Cholinesterase Inhibitors chemistry MeSH
- Kinetics MeSH
- Organophosphates chemistry MeSH
- Oximes chemical synthesis chemistry MeSH
- Pyridinium Compounds chemical synthesis chemistry MeSH
- Drug Design MeSH
- Cholinesterase Reactivators chemical synthesis chemistry MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene MeSH Browser
- Acetylcholinesterase MeSH
- Chemical Warfare Agents MeSH
- Cholinesterase Inhibitors MeSH
- Organophosphates MeSH
- Oximes MeSH
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
- tabun MeSH Browser
Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Among the organophosphates, with the exception of soman, tabun (GA) intoxications are the least responsive to treatment with commercially available therapeutics. A rational design was used to increase reactivation ability and decrease the toxicity of the novel reactivator. (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203) has better properties than previously tested compounds in vitro and, therefore, is a potential candidate for the treatment of GA intoxication in vivo.
References provided by Crossref.org
Brominated oxime nucleophiles are efficiently reactivating cholinesterases inhibited by nerve agents
Acute Toxic Injuries of Rat's Visceral Tissues Induced by Different Oximes
Toxic Injury to Muscle Tissue of Rats Following Acute Oximes Exposure
Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular Docking Study