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肟类化合物K203对神经毒剂抑制的乙酰胆碱酯酶再活化作用的普遍性

Universality of Oxime K203 for Reactivation of Nerve Agent-Inhibited AChE.

作者信息

Kuca Kamil, Hrabinova Martina, Jun Daniel, Musilek Kamil, Penhaker Marek, Krejcar Ondrej, Soukup Ondrej

机构信息

Biomedical Research Center, Uiversity Hospital Hradec Kralove, Hradec Kralove, Czech republic.

出版信息

Med Chem. 2015;11(7):683-6. doi: 10.2174/1573406411666150407154204.

Abstract

Oxime K203 seems to be the most promising oxime in case of reactivation of tabun-inhibited acetylcholinesterase (AChE). Although it was originally developed for treatment of tabun intoxications, it is able to reactivate cholinesterases inhibited by other nerve agents. This study is aimed at the evaluation of its potency in vitro against other nerve agents. For this purpose, sarin, tabun, cyclosarin, soman, VX, Russian VX and DFP were selected as members of the nerve agent family to check its universality. At high concentrations (10(-3) M), oxime K203 reached promising reactivation activity. At low concentrations, relevant for human use (10(-5) M), promising reactivation potency was obtained only with tabun. In conclusion, oxime K203 reactivates other nerve agents-inhibited cholinesterases, however its broad-spectrum reactivation is limited at high, for human not attainable, concentrations only.

摘要

肟K203似乎是在重活化被塔崩抑制的乙酰胆碱酯酶(AChE)方面最有前景的肟。尽管它最初是为治疗塔崩中毒而研发的,但它能够重活化被其他神经毒剂抑制的胆碱酯酶。本研究旨在评估其体外对其他神经毒剂的效力。为此,选择沙林、塔崩、环沙林、梭曼、VX、俄罗斯VX和二异丙基氟磷酸酯作为神经毒剂家族的成员来检验其通用性。在高浓度(10⁻³ M)时,肟K203具有可观的重活化活性。在与人体使用相关的低浓度(10⁻⁵ M)时,仅对塔崩获得了可观的重活化效力。总之,肟K203能重活化被其他神经毒剂抑制的胆碱酯酶,然而其广谱重活化仅在高浓度(对人体而言无法达到)时受限。

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