Monoquaternary pyridinium salts with modified side chain-synthesis and evaluation on model of tabun- and paraoxon-inhibited acetylcholinesterase
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18676153
DOI
10.1016/j.bmc.2008.07.036
PII: S0968-0896(08)00649-4
Knihovny.cz E-resources
- MeSH
- Acetylcholinesterase chemistry drug effects MeSH
- Enzyme Activation drug effects MeSH
- Enzyme Activators chemical synthesis chemistry pharmacology MeSH
- Models, Biological * MeSH
- Cholinesterase Inhibitors pharmacology MeSH
- Rats MeSH
- Molecular Structure MeSH
- Brain enzymology MeSH
- Organophosphates antagonists & inhibitors pharmacology MeSH
- Paraoxon antagonists & inhibitors pharmacology MeSH
- Drug Evaluation, Preclinical MeSH
- Pyridinium Compounds chemical synthesis chemistry pharmacology MeSH
- Drug Design MeSH
- Stereoisomerism MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Enzyme Activators MeSH
- Cholinesterase Inhibitors MeSH
- Organophosphates MeSH
- Paraoxon MeSH
- Pyridinium Compounds MeSH
- tabun MeSH Browser
Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Eighteen monoquaternary reactivators of acetylcholinesterase with modified side chain were developed in an effort to extend the properties of pralidoxime. The known reactivators (pralidoxime, HI-6, obidoxime, trimedoxime, methoxime) and the prepared compounds were tested in vitro on a model of tabun- and paraoxon-inhibited AChE. Monoquaternary reactivators were not able to exceed the best known compounds for tabun poisoning, but some of them did show reactivation better or comparable with pralidoxime for paraoxon poisoning. However, extensive differences were found by a SAR study for various side chains on the non-oxime part of the reactivator molecule.
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