Structural requirements of acetylcholinesterase reactivators
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
- MeSH
- Acetylcholine pharmacology MeSH
- Acetylcholinesterase metabolism MeSH
- Enzyme Activation drug effects MeSH
- Muscarinic Antagonists pharmacology MeSH
- Antidotes pharmacology MeSH
- Atropine pharmacology MeSH
- Chemical Warfare Agents toxicity MeSH
- Cholinesterase Inhibitors toxicity MeSH
- Phosphorylation MeSH
- Humans MeSH
- Neurotransmitter Agents pharmacology MeSH
- Nicotine pharmacology MeSH
- Oximes chemistry metabolism pharmacology MeSH
- Cholinesterase Reactivators chemistry metabolism MeSH
- Receptor, Muscarinic M1 metabolism MeSH
- Binding Sites MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Acetylcholine MeSH
- Acetylcholinesterase MeSH
- Muscarinic Antagonists MeSH
- Antidotes MeSH
- Atropine MeSH
- Chemical Warfare Agents MeSH
- Cholinesterase Inhibitors MeSH
- Neurotransmitter Agents MeSH
- Nicotine MeSH
- Oximes MeSH
- Cholinesterase Reactivators MeSH
- Receptor, Muscarinic M1 MeSH
Nerve agents (sarin, soman, cyclosarin, tabun and VX agent) and pesticides (paraoxon, chlorpyrifos, TEPP) represent extremely toxic group of organophosphorus compounds (OPCs). These compounds inhibit enzyme acetylcholinesterase (AChE, EC 3.1.1.7) via its phosphorylation or phosphonylation at the serine hydroxy group in its active site. Afterwards, AChE is not able to serve its physiological function and intoxicated organism is died due to overstimulation of cholinergic nervous system. The current standard treatment of poisoning with highly toxic OPCs usually consists of the combined administration of anticholinergic drugs (preferably atropine) and AChE reactivators (called "oximes"). Anticholinergic drugs block effects of accumulated neurotransmitter acetylcholine at nicotinic and muscarinic receptor sites, while oximes reactivate AChE inhibited by OPCs. Unfortunately, none from the currently used oximes is sufficiently effective against all known nerve agents and pesticides. Therefore, to find new oximes able to sufficiently reactivate inhibited AChE (regardless of the type of OPCs) is still very important task for medicinal chemistry with the aim to improve the efficacy of antidotal treatment of the acute poisonings mentioned. In this paper, the relationship between chemical structure of AChE reactivators and their ability to reactivate AChE inhibited by several nerve agents and pesticides is summarized. It is shown that there are several structural fragments possibly involving in the structure of proposed AChE reactivators. Finally, an attempt of a future course of new AChE reactivators development is discussed.
References provided by Crossref.org
Strategies for enhanced bioavailability of oxime reactivators in the central nervous system
Trends in the Recent Patent Literature on Cholinesterase Reactivators (2016-2019)
Acetylcholinesterase: The "Hub" for Neurodegenerative Diseases and Chemical Weapons Convention
Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular Docking Study
Amperometric Biosensors for Real Time Assays of Organophosphates
Two step synthesis of a non-symmetric acetylcholinesterase reactivator
