Oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates

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• 作者：Jokanovic ; Milan ; Maksimovic ; Matej ; Kilibarda ; Vesna ; Jovanovic ; Djordje ; Savic ; Dragoslav
• 关键词：Acetylcholinesterase ; Organophosphorus compounds ; Oximes ; Phosphoramidates
• 刊名：Toxicology Letters
• 出版年：1996
• 出版时间：April, 1996
• 年：1996
• 卷：85
• 期：1
• 页码：35-39
• 全文大小：324 K

文摘

The reaction of human erythrocyte acetylcholinesterase (AChE) with a set of structurally related phosphoramidates was studied in order to investigate the properties of phosphorylated enzyme and the effects of 4 oximes PAM-2, TMB-4, HI-6 and BDB-106 on the reactivation of inhibited AChE. Second-order rate constant of the phosphorylation reaction of the compounds towards the active site of AChE ranged between 5.0 × 10² and 4.9 × 10⁶ M⁻¹min⁻¹ and their inhibitory power (I₅₀) was from 7.3 × 10⁻⁵ to 5.7 × 10⁻⁹ M for 20 min incubation at 37°C. The oximes used were weak reactivators of inhibited AChE except for (C₄H₉O)(NH₂)P(O)DCP (DCP, -O-2,5-dichlorphenyl group) and (C₆H₁₃O)(NH₂)P(O)SCH₃ where we have obtained good reactivation. Imidazole oxime BDB-106 proved to be a potent reactivator of tabun-inhibited AChE.