药学学报, 2020, 55(2): 283-288
引用本文:
王书云, 孙富周, 孙义凡, 黄健, 王金辉, 杨宝峰. 维药格蓬脂中三萜类化学成分研究及其抗胆碱酯酶活性评价[J]. 药学学报, 2020, 55(2): 283-288.
WANG Shu-yun, SUN Fu-zhou, SUN Yi-fan, HUANG Jian, WANG Jin-hui, YANG Bao-feng. Triterpenoids from Galbanum of uygur medicine and their anticholinesterase activities[J]. Acta Pharmaceutica Sinica, 2020, 55(2): 283-288.

维药格蓬脂中三萜类化学成分研究及其抗胆碱酯酶活性评价
王书云1,2,3, 孙富周3, 孙义凡4, 黄健2,3, 王金辉2,3, 杨宝峰2
1. 河南大学药学院, 河南 开封 475004;
2. 哈尔滨医科大学药化教研室, 省部共建生物医药工程重点实验室, 黑龙江 哈尔滨 150081;
3. 沈阳药科大学中药学院, 辽宁 沈阳 110016;
4. 深圳弘汇生物医药有限公司, 广东 深圳 518118
摘要:
采用反复硅胶柱色谱、开放ODS柱色谱、重结晶和半制备型HPLC等方法,从维药格蓬脂的甲醇超声提取物中共分离得到8个三萜类化合物。根据波谱数据及理化性质鉴定了化合物的结构,分别为:3β,19α,21α-三羟基-12-烯-28-油酸(1)、苏门树脂脑酸(2)、3β,19α-二羟基-12-烯-28-油酸(3)、齐墩果酸(4)、3β,6β,19α-三羟基-12-烯-28-油酸(5)、19α-羟基齐墩果酮酸(6)、6α-羟基齐墩果酮酸(7)和3α,6α-二羟基-11R,12R-环氧齐墩果烷-28,13α-内酯(8),其中化合物1为新化合物,化合物28首次从该科植物中分离得到。运用改进Ellman法对化合物18进行胆碱酯酶抑制活性筛选,化合物1表现出较强的丁酰胆碱酯酶抑制活性,进一步对其进行了分子对接研究,提示Trp82、His438、Phe329及Ala328四个氨基酸残基是化合物1与丁酰胆碱酯酶结合的关键位点。
关键词:    格蓬脂      三萜      胆碱酯酶抑制活性      分子对接     
Triterpenoids from Galbanum of uygur medicine and their anticholinesterase activities
WANG Shu-yun1,2,3, SUN Fu-zhou3, SUN Yi-fan4, HUANG Jian2,3, WANG Jin-hui2,3, YANG Bao-feng2
1. School of Pharmacy, Henan University, Kaifeng 475004, China;
2. Department of Medicinal Chemistry and Natural Medicine Chemistry(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin 150081, China;
3. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China;
4. Shenzhen Honghui Biopharmaceutical Co., Ltd., Shenzhen 518118, China
Abstract:
Eight triterpenes were isolated from the methanol extract of Galbanum by various chromatographic methods including silica gel, ODS opening column, recrystallization and semi-preparative HPLC. Their structures were determined by spectroscopic methods and physicochemical properties as 3β,19α,21α-trihydroxyl-12-en-28-oic acid (1), sumaresinolic acid (2), 3β,19α-dihydroxyl-12-en-28-oic acid (3), oleanolic acid (4), 3β,6β,19α-trihydroxyl-12-en-28-oic acid (5), 19α-hydroxy oleanonic acid (6), 6α-hydroxy oleanonic acid (7), and (11R,12R)-3α,6α-dihydroxy-epoxyolean-28α,13α-olide (8). Among them, compound 1 is a new compound, while compounds 2-8 were newly isolated from the Apiaceae family. The ability of compounds 1-8 to inhibit cholinesterase was determined with an improved Ellman method. Compound 1 showed strong inhibitory activity against butyrylcholinesterase. The molecular docking results indicated that Trp82, His438, Phe329 and Ala328 played an important role in the binding of compound 1 to butyrylcholinesterase.
Key words:    Galbanum    triterpenes    cholinesterase inhibition activities    molecular docking   
收稿日期: 2019-06-18
DOI: 10.16438/j.0513-4870.2019-0484
基金项目: 国家“重大新药创制”科技重大专项(2018ZX09305005).
通讯作者: 王金辉,Tel/Fax:86-451-86685745,E-mail:wangjinhui@hrbmu.edu.cn
Email: wangjinhui@hrbmu.edu.cn
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