Reactivation of VX-inhibited AChE by novel oximes having two oxygen atoms in the linker

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• 作者：Kamil Kuca ; Jiri Cabal ; Daniel Jun ; Kamil Musilek ; Ondrej Soukup ; Miroslav Pohanka ; Jaroslav Pejchal ; Kyung-Ae Oh ; Garp Yeol Yang ; Young-Sik Jung
• 关键词：Cholinesterase ; Nerve agent ; VX ; Reactivator ; Oxime ; HI-6
• 刊名：Environmental Toxicology and Pharmacology
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：30
• 期：1
• 页码：85-87
• 全文大小：210 K

文摘

Two newly developed AChE reactivators possessing two oxime groups in 4-position of the pyridinium rings with linkers CH₂O(CH₂)₂OCH₂ and CH₂O(CH₂)₄OCH₂ were tested for their potency to reactivate VX-inhibited AChE. Their reactivation potency was compared with currently available oximes such as pralidoxime, obidoxime and HI-6. Appropriate constants (affinity towards the intact and inhibited enzyme, reactivation rate) characterizing the reactivation process were determined. According to the data obtained, a new oxime with CH₂O(CH₂)₂OCH₂ linker reached as high reactivation potency as HI-6. The percentage of reactivation of the oxime with CH₂O(CH₂)₂OCH₂ linker was comparable to that of obidoxime at a concentration 10⁻³ M. Hence, these oximes may be worthy of future development for the treatment of nerve agent intoxications, especially, with lipophilic agents such as soman and cyclosarin.