海洋中药厚藤中柚皮素(naringenin)衍生物合成及胆碱酯酶抑制活性研究  

Study on synthesis of naringenin derivatives and cholinesterase inhibitory activity in marine Chinese medicine

作　　者：朱玉霞 张玲建 胡懿鸣 刘卫华 关丽萍 林琳 Yuxia Zhu;Lingjian Zhang;Yiming Hu;Weihua Liu;Liping Guan;Lin Lin(The College of Food and Pharmacy,Zhejiang Ocean University,Zhoushan 316022,Zhejiang,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：《Journal of Chinese Pharmaceutical Sciences》2023年第8期636-644,共9页中国药学（英文版）

基　　金：Zhejiang Provincial University Student Science and Technology Innovation Activity Plan and New Seedling Talent Plan(Grant No.2021R411)。

摘　　要：本文以柚皮素(naringenin)为先导化合物,采用新药设计的原理,设计合成一系列查尔酮衍生物并对其进行AChE和BuChE的抑制活性研究。市售的邻羟基苯甲醛与丙烯醛在K2CO3催化下生成苯并吡喃-3-甲醛中间体。苯并吡喃-3-甲醛与取代的苯乙酮经过Claisen-Schmidt反应得到目标化合物。采用改进的Ellmańs法测定查尔酮化合物对AChE和BuChE的抑制活性。8个化合物均显示出一定的抑制AChE和BuChE的活性,其中化合物2d显示出比较高的抑制胆碱酯酶的活性。分子对接结果表明,2d与AChE和BuChE有明显的相互作用.本实验研究表明具有香豆素的查尔酮化合物可能是发现具有潜在抗AD新先导物的一个途径。This paper describes the design and synthesis of a series of chalcone derivatives based on naringenin as the lead compound.The compounds were evaluated for their activities against AChE and BuChE using principles of new drug design.The intermediate benzopyran-3-formaldehyde was synthesized from commercial ortho-hydroxybenzaldehyde and acrolein using K2CO3 as a catalyst.The target compounds were obtained through the Claisen-Schmidt reaction of benzopyran-3-formaldehyde and substituted acetophenone.The inhibitory effects of the chalcone compounds against AChE and BuChE were determined using Ellman’s method.Eight compounds showed certain inhibitory activities against AChE and BuChE,with compound 2d exhibiting higher activity against cholinesterase.Molecular docking studies revealed that 2d had a significant interaction with AChE and BuChE.This study suggested that chalcone compounds,including coumarin,might provide a potential pathway for discovering new anti-AD precursors.

关 键 词：厚藤 柚皮素 查尔酮衍生物 合成 胆碱酶抑制剂 

分 类 号：R916[医药卫生—药学]