Bisquaternary pyridinium oximes: Comparison of in vitro reactivation potency of compounds bearing aliphatic linkers and heteroaromatic linkers for paraoxon-inhibited electric eel and recombinant human acetylcholinesterase
作者:Sandip B. Bharate、Lilu Guo、Tony E. Reeves、Douglas M. Cerasoli、Charles M. Thompson
DOI:10.1016/j.bmc.2009.11.052
日期:2010.1
bearing aliphatic linkers were synthesized and evaluated for their in vitro reactivation potency against paraoxon-inhibited electric eel acetylcholinesterase (EeAChE) and recombinant human acetylcholinesterase (rHuAChE). Results herein indicate that most of the compounds are better reactivators of EeAChE than of rHuAChE. The reactivation potency of two different classes of compounds with varying linker
肟再活化剂是 OP(有机磷)中毒后处理的首选药物,广泛用于 OP 抑制的胆碱酯酶的机械和动力学研究。本研究的目的是评估新的肟化合物重新激活被 OP 对氧磷抑制的乙酰胆碱酯酶 (AChE)。合成了几种新的带有杂环接头的双季吡啶肟以及一些已知的带有脂肪族接头的双季吡啶肟,并评估了它们对对氧磷抑制电鳗乙酰胆碱酯酶 (EeAChE) 和重组人乙酰胆碱酯酶 (rHuAChE) 的体外再激活效力。本文的结果表明,大多数化合物是 EeAChE 比 rHuAChE 更好的再活化剂。比较了具有不同接头链的两类不同化合物的再活化效力,并观察到连接链的结构是再活化剂活性的重要因素。在较高浓度(10-3 M),带有脂肪族接头的化合物比带有杂环接头的化合物表现出更好的再活化。有趣的是,具有杂环接头的肟在较高浓度(10 -3 M)下抑制AChE ,而在较低浓度(10 -4 M 和10 -5 M)下它们的再激活