Molecular modeling-guided optimization of acetylcholinesterase reactivators: A proof for reactivation of covalently inhibited targets
نویسندگان
چکیده
منابع مشابه
Reactivation 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 کاملThe Length Dependent Activity of Oximes on Reactivation of Tabun Inhibited Acetylcholinesterase; A Theoretical Study
In this work, the effect of ligand's length on interaction energy of six oximes, A [2-(hydroxyimino)-N-((1-(2-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)acetamide], B [2-(hydroxyimino)-N-((1-(3-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methyl)acetamide], C [2-(hydroxyimino)-N-((1-(4-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)but...
متن کاملIn silico pharmacophore model for tabun-inhibited acetylcholinesterase reactivators: a study of their stereoelectronic properties.
Organophosphorus (OP) nerve agents that inhibit acetylcholinesterase (AChE; EC 3.1.1.7) function in the nervous system, causing acute intoxication. If untreated, death can result. Inhibited AChE can be reactivated by oximes, antidotes for OP exposure. However, OP intoxication caused by the nerve agent tabun (GA) is particularly resistant to oximes, which poorly reactivate GA-inhibited AChE. In ...
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 کاملthe length dependent activity of oximes on reactivation of tabun inhibited acetylcholinesterase; a theoretical study
in this work, the effect of ligand's length on interaction energy of six oximes, a [2-(hydroxyimino)-n-((1-(2-(2-((hydroxyimino)methyl)-1h-imidazol-1-yl)ethyl)-1h-1,2,3-triazol-4-yl)methyl)acetamide], b [2-(hydroxyimino)-n-((1-(3-(2-((hydroxyimino)methyl)-1h-imidazol-1-yl)propyl)-1h-1,2,3-triazol-4-yl)methyl)acetamide], c [2-(hydroxyimino)-n-((1-(4-(2-((hydroxyimino)methyl)-1h-imidazol-1-y...
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ژورنال
عنوان ژورنال: European Journal of Medicinal Chemistry
سال: 2021
ISSN: 0223-5234
DOI: 10.1016/j.ejmech.2021.113286