光甘草定的合成及抑制AChE与BuChE的研究  

Study on Synthesis and Pharmacological Activities of Glabridin

作　　者：贺志文 沈烨相 刘卫华 王秋实 胡懿鸣 张玲建 朱玉霞 关丽萍 蒋永俊 HE Zhi-wen;SHEN Ye-xiang;LIU Wei-hua(School of Food and Pharmacy of Zhejiang Ocean University,Zhoushan 316022,China)

机构地区：[1]浙江海洋大学食品与药学学院,浙江舟山316022

出　　处：《浙江海洋大学学报（自然科学版）》2023年第1期82-87,共6页Journal of Zhejiang Ocean University：Natural Science

基　　金：浙江省自然科学基金(LGF22H300005);浙江省虚拟仿真实验教学项目(2021年);浙江省公益技术应用研究计划(2017C33131);浙江省大学生科技创新活动计划暨新苗人才计划(2021R411)。

摘　　要：以价格低廉的7-羟基香豆素为起始原料与3-甲基-3-氯-1-丁炔反应形成炔醚,随后在所得α,β-不饱和化合物的α位引入溴原子,经过重排、Szuki偶联作为核心反应构建关键中间体(Ⅳ),还原共轭双键成醚、脱除甲基共六步反应,产物经过HPLC、^(1)H-NMR、^(13)C-NMR和质谱确定结构,并对光甘草定进行胆碱酯酶活性研究。实验结果表明:合成后的光甘草定对AChE与BuChE有一定的抑制作用,使用动态分子对接,探索了光甘草定与胆碱酯酶之间的相互作用,并确定了结合口袋,模拟表明,光甘草定与胆碱酯酶结合紧密,与体外酶活性实验结果相一致。Inexpensive 7-hydroxycoumarin was used as the starting material to react with 3-methyl-3-butyn-1-ol to form an alkynyl ether,and then introduce a bromine atom into theαposition of the obtainedα,β-unsaturated compound.After rearrangement and Szuki coupling as the core reaction,the key intermediate(IV)was constructed,and the conjugated double bond was reduced to form ether,and the methyl group was removed in a total of six steps.The structure of the product was confirmed by HPLC,^(1)H-NMR,^(13)C-NMR and MS,and the effect of glabridin with cholinesterase were studied.Results showed that the synthesized glabridin with AchE and BuChE has certain inhibitory effect.In dynamic molecular docking,the result explores glabridin possesses the interaction between cholinesterase,and determine the combination pocket.Simulation shows that the light liquorice and cholinesterase tightly bound,which is consistent with the results of enzyme activity in vitro.

关 键 词：光甘草定 保护神经系统 抗阿尔兹海默症 抗胆碱酯酶 分子对接 

分 类 号：R914.5[医药卫生—药物化学]