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

doi:10.5246/jcps.2023.08.053

摘要/Abstract

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。

关键词: 厚藤, 柚皮素, 查尔酮衍生物, 合成, 胆碱酶抑制剂

Abstract:

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.

Key words: Ipomoea pes-caprae, Naringenin, Chalcone derivatives, Synthesis, Cholinesterase inhibitors

Supporting: /attached/file/20230904/20230904181042_401.pdf

朱玉霞, 张玲建, 胡懿鸣, 刘卫华, 关丽萍, 林琳. 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[J]. 中国药学(英文版), 2023, 32(8): 636-644.

Yuxia Zhu, Lingjian Zhang, Yiming Hu, Weihua Liu, Liping Guan, Lin Lin. Study on synthesis of naringenin derivatives and cholinesterase inhibitory activity in marine Chinese medicine[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(8): 636-644.

图/表 4

Figure 1. Design strategy and the synthetic route for chalcone compound.

Table 1. The relevant physical data of Chalcone derivatives 2a–2h.

Table 2. Inhibitory effects of AChE and BuChE by chalcone compounds.

Figure 2. 2d docked with AchE molecules (a and b); 2d docked with BuChE molecules (c and d).

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