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

Triterpenoids from Galbanum of uygur medicine and their anticholinesterase activities

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2~8首次从该科植物中分离得到。运用改进Ellman法对化合物1~8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。

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(11 R,12 R)-3α,6α-dihydroxy-epoxyolean-28α,13α-olide(8).Among them,compound 1 is a new compound,while compounds2-8 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.