含1,3,4-噁二唑的喹啉衍生物的合成、抗AChE活性及分子对接研究  

Synthesis,Biological Evaluation and Molecular docking of Quinoline Derivatives Containing 1,3,4-Oxadiazole as AChE Inhibitor

作　　者：张敏杰 陈贵芬 陈娅芳 於祥 杨武德 Zhang Minjie;Chen Guifen;Chen Yafang;Yu Xiang;Yang Wude(College of pharmacy,Guizhou University of Traditional Chinese Medicne,Guiyang,550025)

机构地区：[1]贵州中医药大学药学院,贵阳550025

出　　处：《化学通报》2023年第10期1269-1273,I0001,共6页Chemistry

基　　金：国家自然科学基金项目(82260833);贵州省自然科学基金项目(黔科合基础[2020]1Y070)资助。

摘　　要：为研发新型乙酰胆碱酯酶抑制剂,本文通过碘介导环化反应合成了一系列含1,3,4-噁二唑的喹啉衍生物,并通过熔点和核磁共振谱确定了其结构。在1μmol/mL浓度下,对这些衍生物抗乙酰胆碱酯酶活性进行了初步的生物测定。结果表明,化合物4b和4j具有中等的抑制活性,抑制率分别为79.18%和78.46%。初步构效关系分析表明,在目标化合物的1,3,4-噁二唑环上引入杂环可以提高其活性。分子对接研究表明,化合物4b和4j和乙酰胆碱酯酶的催化活性中心部位显著结合。In continuation of our research aimed at discovery and development of new acetylcholinesterase(AChE)inhibitor,a series of quinoline derivatives containing 1,3,4-oxadiazole were synthesized via iodine mediated cyclization and their structures were confirmed by melting point and NMR.Preliminary bioassay of these derivatives"activities against AChE was also evaluated in vitro at the concentration of 1μmol/mL.The result showed that compounds 4b and 4j had moderate inhibitory activities with inhibitory rates of 79.18%and 78.46%,respectively.The preliminary structure-activity relationship revealed that introduction of heterocyclic rings on 1,3,4-oxadiazole of target compounds could enhance their activities.Molecular docking study suggested that compounds 4b and 4j possessed an optimal docking pose with interactions inside AChE.

关 键 词：喹啉 1 3 4-噁二唑 乙酰胆碱酯酶抑制剂 合成 分子对接 

分 类 号：O626[理学—有机化学] TQ460.1[理学—化学]