A new group of monoquaternary reactivators of acetylcholinesterase inhibited by nerve agents
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Acetylcholinesterase metabolism MeSH
- Kinetics MeSH
- Ligands MeSH
- Molecular Structure MeSH
- Nitrophenols metabolism MeSH
- Oximes chemical synthesis pharmacology MeSH
- Pralidoxime Compounds chemistry MeSH
- Pyridinium Compounds chemistry MeSH
- Cholinesterase Reactivators chemical synthesis pharmacology MeSH
- Drug Synergism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 4-hydroxyiminomethyl-1-methylpyridinium iodide MeSH Browser
- 4-nitrophenyl acetate MeSH Browser
- Acetylcholinesterase MeSH
- Ligands MeSH
- Nitrophenols MeSH
- Oximes MeSH
- pralidoxime MeSH Browser
- Pralidoxime Compounds MeSH
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
Reactivators of acetylcholinesterase (AChE; EC 3.1.1.7) are able to treat intoxication by organophosphorus compounds, especially with pesticides or nerve agents. Owing to the fact that there exists no universal "broad-spectrum" reactivator of organophosphates-inhibited AChE, many laboratories have synthesized new AChE reactivators. Here, we synthesized five new and three previously known quaternary monopyridinium oximes as potential reactivators of AChE inhibited by nerve agents. Potencies to cleave p-nitrophenyl acetate (PNPA), which is commonly used as a model substrate of nerve agents, were measured. Their cleaving potencies were compared with 4-PAM (4-hydroxyiminomethyl-1-methylpyridinium iodide), which is derived from the structure of the currently used AChE-reactivator 2-PAM (2-hydroxyiminomethyl-1-methylpyridinium iodide). Three newly synthesized oximes achieved similar nucleophilicity at the similar pKa according to 4-PAM, which is very promising for using these derivatives as AChE reactivators.
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