Monooxime reactivators of acetylcholinesterase with (E)-but-2-ene linker: preparation and reactivation 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
Grant support
G0400930
Medical Research Council - United Kingdom
PubMed
17764957
DOI
10.1016/j.bmc.2007.08.002
PII: S0968-0896(07)00696-7
Knihovny.cz E-resources
- MeSH
- Acetylcholinesterase drug effects MeSH
- Antidotes chemical synthesis chemistry pharmacology MeSH
- Cholinesterase Inhibitors poisoning MeSH
- Rats MeSH
- Organophosphates antagonists & inhibitors pharmacology MeSH
- Oximes chemical synthesis chemistry pharmacology MeSH
- Paraoxon antagonists & inhibitors pharmacology MeSH
- Drug Design MeSH
- Cholinesterase Reactivators chemical synthesis chemistry pharmacology 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
- Antidotes MeSH
- Cholinesterase Inhibitors MeSH
- Organophosphates MeSH
- Oximes MeSH
- Paraoxon MeSH
- Cholinesterase Reactivators MeSH
- tabun MeSH Browser
Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Fifteen new monooxime reactivators of acetylcholinesterase with a (E)-but-2-ene linker were developed in an effort to extend the properties of K-oxime (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). The known reactivators (pralidoxime, HI-6, obidoxime, K075, K203) and the new compounds were tested in vitro on a model of tabun- and paraoxon-inhibited AChE. Monooxime reactivators were not able to exceed the best known compounds for tabun poisoning, but some of them did show reactivation comparable with known compounds for paraoxon poisoning. However, extensive differences were found by a SAR study for various substitutions on the non-oxime part of the reactivator molecule.
References provided by Crossref.org
Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular Docking Study
