Design, Synthesis and Biological Evaluation of α-Aminophosphonate Derivatives Containing a Pyrazole Moiety
Design, Synthesis and Biological Evaluation of α-Aminophosphonate Derivatives Containing a Pyrazole Moiety
复制标题
DOI：
10.1248/cpb.c16-00622
复制
发表时间：
2016-12-01
影响因子：
1.7
通讯作者：
Cao, Hai-Qun
中科院分区：
文献类型：
--
作者：
Ren, Zi-Li;Zhang, Jing;Cao, Hai-Qun
乙酰胆碱酯酶（Acetylcholinesterase，AChE）是存在于生物体中枢神经系统的一种关键酶。作为杀虫剂的有机磷农药（OPs）是AChE抑制剂，在农业中得到了广泛的应用。设计并合成了一系列新型含吡唑结构的有机磷农药。生物活性测定结果表明，化合物4 e在0.1mg/L浓度下对小菜蛾幼虫有81%的毒杀活性，且随着剂量的增加，化合物4 e对AChE的抑制作用明显增强。利用Discovery Studio（DS）对化合物4 e与果蝇AChE（DinAChE，PDB code：1 QO 9）的三维X-射线结构进行了分子对接，结合模型显示标题结构紧密嵌入DmAChE的结合位点。因此，我们建议化合物4 e可以作为一种新的乙酰胆碱酯酶抑制剂，可以利用作为一个新的杀虫药物。
Acetylcholinesterase (AChE) is a key enzyme which present in the central nervous system of living organisms. Organophosphorus pesticides (OPs) that serve as insecticides are AChE inhibitors which have been used widely in agriculture. A series of novel OPs containing pyrazole moiety have been designed and synthesized. The biological evaluation indicated compound 4e appeared 81% larvicidal activity against Plutella xylostella at the concentration of 0.1mg/L and the inhibition of AChE by compound 4e was distinctly enhanced with the increasing doses. Molecular docking of compound 4e into the three dimensional X-ray structure of the Drosophila melanogaster AChE (DinAChE, PDB code: 1QO9) was carried out utilizating the Discovery Studio (DS), the binding model revealed that the title structure was tightly embedded in the binding sites of DmAChE. Therefore, we suggest that compound 4e may serve as a novel AChE inhibitor that can be utilized as a new insecticidal drug.