车前草中黄酮类成分结构和性质的理论研究  

Theoretical Study on the Structures and Properties of Flavonoids in Plantain

作　　者：黄罗仪 翁约约 黄旭慧 王朝杰 HUANG Luoyi;WENG Yueyue;HUANG Xuhui;WANG Chaojie(School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China;Department of Pharmacy,Wenzhou Central Hospital,Wenzhou 325000,China;Department of Pharmacy,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325035,China)

机构地区：[1]温州医科大学药学院,温州325035 [2]温州市中心医院药剂科,温州325000 [3]温州医科大学附属第二医院药学部,温州325035

出　　处：《高等学校化学学报》2021年第9期2752-2765,共14页Chemical Journal of Chinese Universities

基　　金：浙江省中医药科技计划项目(批准号:2020ZB141);浙江省自然科学基金(批准号:LY16B070006);国家自然科学基金(批准号:21177098)资助.

摘　　要：采用密度泛函理论中ωB97XD/6-311+G(2d,p)方法对车前草中的黄酮类化合物进行量化计算研究,探讨了该类化合物的构效关系.首先研究了13种车前草中提取的黄酮类化合物(1~13)和已成药的二氢杨梅素(14)的几何结构、谱学性质及电子结构,再运用概念密度泛函理论进行反应指数分析,最后利用药代动力学平台开展了成药性评价.根据几何结构的分析结果初步推测14种黄酮类化合物的抗氧化能力强弱顺序为10>12≈7>13>6>4>14≈9≈8>11>5>3≈2>1.核磁共振拟合结果表明,利用该方法得到的核磁位移理论值与实验值吻合度较高(R2>0.95).分子表面静电势图显示,14种黄酮类化合物的静电势的极小值点都位于羰基氧附近,极大值点都位于羟基氢附近,且B环上对位羟基的极大值>C环和A环羟基极大值.全局反应性描述符结果显示,化合物1,2,4,11和12的化学势较低,电负性、亲电指数和硬度较高,说明这5种化合物的稳定性和反应性较好.通过局部反应性描述符进一步预测了14种黄酮类化合物的亲核/亲电反应位点.药代动力学结果显示,化合物1,3,4,6,12和13的成药性和药代动力学活性较好.研究结果表明,化合物4和12最有成药潜力,可进行更深入的实验研究.TheωB97XD/6-311+G(2d,p)method in Density Functional Theory(DFT)was used to quantitatively calculat the flavonoids in plantain,to explore the structure-activity relationship of this class of compounds and to studied the geometric structure,spectral properties and electronic structure of 13 kinds of flavonoids from plantain and dihydromyricetin.Then the reactivity indexes analysis were carried out using conceptual density functional theory.At last the pharmacokinetic platform was used to evaluate the drug-like.Based on the results of the geometry analysis,it was initially estimated that the antioxidant order of 14 flavonoids was:10>12≈7>13>6>4>14≈9≈8>11>5>3≈2>1.The fitting result of nuclear magnetic resonance spectroscopy(NMR)showed that the theoretical value of NMR obtained by this method was in good agreement with the experimental value(R2>0.95).The results of electrostatic potential map on molecular surface showed that the minimum points of electrostatic potential of 14 flavonoids were near carbonyl oxygen,while the maximum points were near hydroxyl hydrogen.It was found that the maximum values on the opposite hydroxyl groups on the B ring were greater than C and A rings.According to the results of the global reactivity descriptor,it was found that the chemical potentials of compounds 1,2,4,11 and 12 were lower,and the electronegativity,electrophilic index while hardness were higher,which indicating these 5 compounds had better stability and reactivity.The local reactivity descriptor further identified the nucleophilic/electrophilic reaction sites of 14 compounds.Finally,the pharmacokinetic results screened out that compounds 1,3,4,6,12 and 13 may be as possible alternatives to dihydromyricetin drug.In the end,compounds 4 and 12 were found to have the most potential as medicines,and further experimental studies could be carried out.

关 键 词：车前草 黄酮类 抗氧化活性 密度泛函理论 

分 类 号：O656.4[理学—分析化学] R917[理学—化学]