具有乙酰胆碱酯酶抑制活性间苯三酚衍生物的发现及其作用机制研究
结题报告
批准号:
31970377
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
秦徐杰
学科分类:
植物化学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
秦徐杰
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中文摘要
阿尔茨海默病是最为常见的神经退行性疾病之一,而乙酰胆碱酯酶是阿尔茨海默病的重要靶标。申请人近期发现桃金娘、大叶桉和红千层的提取物具有显著的乙酰胆碱酯酶抑制活性,通过活性追踪方法,从中分离到系列新颖间苯三酚衍生物。其中六个分子表现出优异的乙酰胆碱酯酶抑制活性,尤其是化合物rhodomyrtosone A与阳性对照药加兰他敏活性相当,并推测了其与乙酰胆碱酯酶的作用位点。本项目拟通过活性追踪手段,对这三种植物开展深入的物质基础研究,对活性分子进行合成和衍生,获得多样性间苯三酚衍生物,以期获得活性更强的分子并开展构效关系;结合分子对接和分析化合物与乙酰胆碱酯酶共晶复合物的技术手段,阐明活性分子的作用机制,并完成强活性化合物对阿尔茨海默病大鼠小脑的神经保护作用评价。本项目的开展不仅有利于桃金娘科植物的深入开发,而且有望获得用于治疗阿尔茨海默病的先导化合物。
英文摘要
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, whereas acetylcholinesterase (AChE) is an important target for AD. Recently, the crude extacts of Rhodomyrtus tomentosa, Eucalyptus robusta, and Callistemon salignus were revealed to exhibit significant AChE inhibitory effects, and a series of novel phloroglucinol derivatives have been obtained from above-mentioned species by means of a bioactivity-guided method. Six of these isolates showed excellent AChE inhibitory activities, especially the activity of rhodomyrtosone A was comparable to that of the positive control drug galantamine, and its possible action sites with AChE were also speculated. With the aim to obatin diversified phloroglucinol derivatives, this project intends to perform in-depth material basis research of these three species with the aid of a bioactivity-guided method and the bioactive molecules will be synthesized and derivated so as to get the molecules with sronger activities and the structure-activity relationships of these comounds will also be carried out. Combined with molecular docking, analysis of co-crystal complex of compound and AChE will be used to clarify the action mechanism of bioactive molecules, and the neuroprotective effects of compounds with stronger AChE inhibitory activities on the rats cerebellum with alzheimer's disease will also be evaluated. The implementation of this project will not only conducive to the in-depth development of Myrtaceae plants, and the lead compounds that used for the treatment of AD will also be expected to be obtained.
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DOI:10.1016/j.bioorg.2020.104519
发表时间:2020-11
期刊:Bioorganic chemistry
影响因子:5.1
作者:Xu-Jie Qin;Hui Liu;Pan-pan Li;W. Ni;Li He;Afsar Khan;X. Hao;Haiyang Liu
通讯作者:Xu-Jie Qin;Hui Liu;Pan-pan Li;W. Ni;Li He;Afsar Khan;X. Hao;Haiyang Liu
Polymethylated Phloroglucinol Meroterpenoids from Rhodomyrtus tomentosa and Their Antibacterial and Acetylcholinesterase Inhibitory Effects
毛红桃多甲基化间苯三酚小萜类化合物及其抗菌和乙酰胆碱酯酶抑制作用
DOI:10.1002/cbdv.202000489
发表时间:2020
期刊:Chemistry & Biodiversity
影响因子:2.9
作者:Hui Liu;Ping Li;Li‐Sha Bi;Wenjuan Wu;Huan Yan;Li He;Xu;Haiyang Liu
通讯作者:Haiyang Liu
DOI:10.1016/j.bioorg.2021.105404
发表时间:2021-10
期刊:Bioorganic chemistry
影响因子:5.1
作者:Mu-Yuan Yu;Simei Liu;Hui Liu;Qingfei Meng;Xu-Jie Qin;Haiyang Liu
通讯作者:Mu-Yuan Yu;Simei Liu;Hui Liu;Qingfei Meng;Xu-Jie Qin;Haiyang Liu
DOI:10.1016/j.phytochem.2022.113394
发表时间:2022-08
期刊:Phytochemistry
影响因子:3.8
作者:Mu-Yuan Yu;Simei Liu;E-E Luo-E;Qing Jin;Hui Liu;Haiyang Liu;Xiao-Dong Luo;Xu-Jie Qin
通讯作者:Mu-Yuan Yu;Simei Liu;E-E Luo-E;Qing Jin;Hui Liu;Haiyang Liu;Xiao-Dong Luo;Xu-Jie Qin
DOI:10.1016/j.bioorg.2020.104127
发表时间:2020-10
期刊:Bioorganic chemistry
影响因子:5.1
作者:Liu H;He XZ;Feng MY;Yuan-Zeng;Rauwolf TJ;Shao LD;Ni W;Yan H;Porco JA Jr;Hao XJ;Qin XJ;Liu HY
通讯作者:Liu HY
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