Structure-Based Optimization of Nonquaternary Reactivators of Acetylcholinesterase Inhibited by Organophosphorus Nerve Agents
نویسندگان
چکیده
منابع مشابه
New Cinchona Oximes Evaluated as Reactivators of Acetylcholinesterase and Butyrylcholinesterase Inhibited by Organophosphorus Compounds.
For the last six decades, researchers have been focused on finding efficient reactivators of organophosphorus compound (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In this study, we have focused our research on a new oxime scaffold based on the Cinchona structure since it was proven to fit the cholinesterases active site and reversibly inhibit their activity. Thr...
متن کاملDocking Studies, Synthesis, and In-vitro Evaluation of Novel Oximes Based on Nitrones as Reactivators of Inhibited Acetylcholinesterase
Acetylcholinesterase has important role in synaptic cleft. It breaks down the acetylcholineatcholinergic synapsesand terminates the cholinergic effects. Some chemical agents likeorganophosphorus compounds (OPCs) including nerve agents and pesticides react withacetylcholinesteraseirreversibly. They inhibit normal biological enzyme action and resultin accumulation of acetylcholineand show toxic e...
متن کاملDocking Studies, Synthesis, and In-vitro Evaluation of Novel Oximes Based on Nitrones as Reactivators of Inhibited Acetylcholinesterase
Acetylcholinesterase has important role in synaptic cleft. It breaks down the acetylcholineatcholinergic synapsesand terminates the cholinergic effects. Some chemical agents likeorganophosphorus compounds (OPCs) including nerve agents and pesticides react withacetylcholinesteraseirreversibly. They inhibit normal biological enzyme action and resultin accumulation of acetylcholineand show toxic e...
متن کاملReactivation of Human Acetylcholinesterase and Butyrylcholinesterase Inhibited by Leptophos-Oxon with Different Oxime Reactivators in Vitro
We have evaluated in vitro the potency of 23 oximes to reactivate human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) inhibited by racemic leptophos-oxon (O-[4-bromo-2,5-dichlorophenyl]-O-methyl phenyl-phosphonate), a toxic metabolite of the pesticide leptophos. Compounds were assayed in concentrations of 10 and 100 μM. In case of leptophos-oxon inhibited AChE,...
متن کاملPrediction of a new broad-spectrum reactivator capable of reactivating acetylcholinesterase inhibited by nerve agents
A methodology combining molecular structure represented by fragments, and artificial neural network (ANN) was applied for the prediction of a new acetylcholinesterase (AChE; EC 3.1.1.7) reactivator. We searched for a new structure of the AChE reactivator with the capability of reactivating AChE inhibited by almost all actual nerve agents. For this purpose, we have tested in vitro seventeen pote...
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ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2018
ISSN: 0022-2623,1520-4804
DOI: 10.1021/acs.jmedchem.8b00592