School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur, C.G., 492010, India.
Process Technology Development Division, Defence Research & Development Establishment, Jhansi Road, Gwalior, M.P., 474002, India.
Chem Biol Interact. 2016 Nov 25;259(Pt B):85-92. doi: 10.1016/j.cbi.2016.04.034. Epub 2016 Apr 29.
Post-treatment of organophosphate (OP) poisoning involves the application of oxime reactivator as an antidote. Structurally different oximes are widely studied to examine their kinetic and mechanistic behavior against OP-inhibited cholinesterase enzyme. A series of structurally related 1,3-disubstituted-2-[(hydroxyiminomethyl)alkyl]imidazolium halides (5a-5e, 9a-9c) were synthesized and further evaluated for their in-vitro reactivation ability to reactivate sarin- and VX-inhibited human acetylcholinesterase (hAChE). The observed results were compared with the reactivation efficacy of standard reactivators; 2-PAM, obidoxime and HI-6. Amongst the synthesized oximes, 5a, 9a and 9b were found to be most potent reactivators against sarin-inhibited hAChE while in case of VX only 9a exhibited comparable reactivity with 2-PAM. Incorporation of pyridinium ring to the imidazole ring resulted in substantial increase in the reactivation strength of prepared reactivator. Physicochemical properties of synthesized reactivators have also been evaluated.
有机磷（OP）中毒的治疗后处理涉及应用肟类重活化剂作为解毒剂。广泛研究了结构不同的肟，以检查它们针对 OP 抑制的胆碱酯酶的动力学和机制行为。合成了一系列结构相关的 1,3-二取代-2-[(羟亚氨基甲基)烷基]咪唑𬭩卤化物（5a-5e、9a-9c），并进一步评估了它们对沙林和 VX 抑制的人乙酰胆碱酯酶（hAChE）的体外重活化能力。观察到的结果与标准重活化剂；2-PAM、obidoxime 和 HI-6 的重活化功效进行了比较。在所合成的肟中，5a、9a 和 9b 被发现是针对沙林抑制的 hAChE 的最有效重活化剂，而对于 VX，只有 9a 表现出与 2-PAM 相当的反应性。将吡啶环引入咪唑环导致所制备的重活化剂的重活化强度大大增加。还评估了合成重活化剂的物理化学性质。
