甘草皂苷类化合物结构与保肝活性关系的DFT研究  

Density functional theory study on the relationship between structure and hepatoprotective activity of saponins from licorice

作　　者：刘靖丽[1] 闫浩 王钰莹 王文亮[2] LIU Jing-li;YAN Hao;WANG Yu-ying;WANG Wen-liang(College of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China;School of Chemistry and Chemical Engineering,Shaanxi Normal University,Xi’an 710119,China)

机构地区：[1]陕西中医药大学药学院,咸阳712046 [2]陕西师范大学化学化工学院,西安710119

出　　处：《天然产物研究与开发》2020年第9期1515-1521,共7页Natural Product Research and Development

基　　金：陕西省教育厅项目(17JK0199);陕西省高校科协青年人才托举计划(20170406)。

摘　　要：三萜皂苷类化合物是中药甘草保肝作用的主要药效物质。本文以甘草中的三种皂苷类化合物甘草酸、单葡萄糖醛基甘草次酸和甘草次酸为研究对象,采用密度泛函理论方法(DFT)在B3LYP/6-31+G*水平上,对三萜皂苷类化合物进行量子化学计算。依据化合物的几何结构、NPA电荷、偶极矩、溶剂化能和前线轨道能等参数,分析甘草中皂苷类化合物的结构与保肝活性之间的关系,以期对中药甘草的深入研究与开发提供理论基础。计算结果表明,三种甘草皂苷类化合物的活性部位在五环三萜上,而糖环不是其药理活性部位,但是糖环的结构和数目会影响药物分子的理化性质。根据前线分子轨道能级之差ΔE值可知,三种化合物的保肝活性顺序为:GA>GAMG>GL。Triterpenoid saponins are the main components of licorice,which have extensive biological and pharmacological activities,including hepatoprotective,antiviral and anti-inflammatory effects.In order to study the relationship between the structure and hepatoprotective activity of three saponins,the density functional theory(DFT)B3LYP method with 6-31+G*basis set was used to optimize the structure of glycyrrhizin(GL),glycyrrhetic acid monoglucuronide(GAMG)and glycyrrhetinic acid(GA).The properties of triterpenoid saponins have been discussed in detail based on their molecular structures,NPA charges,dipole moments,solvation energies and the energies of the frontier molecular orbitals.The results showed that the active sites of the three saponins were pentacyclic triterpenes,while the sugar ring was not the pharmacologically active site.However,the structure and the number of sugar ring would affect the physicochemical properties of drug molecules.The results showed that the frontier molecule orbitals were important for hepatoprotective activity,the lower energy gap between HOMO and LUMOΔE(LUMO-HOMO),the stronger activity of the compounds would be.As a result,it was revealed that the hepatoprotective activity of the compounds goes along with the series GA>GAMG>GL.The calculated results were in good agreement with the experimental results.

关 键 词：甘草酸 甘草次酸 单葡萄糖醛基甘草次酸 DFT 

分 类 号：O641[理学—物理化学]