黄酮类衍生物的合成及对黄嘌呤氧化酶活性的影响  

Synthesis of flavonoid derivatives and effect on activity of xanthine oxidase

作　　者：谢珺 苗菁 崔杏 王建塔 王聪 汤磊 XIE Jun;MIAO Jing;CUI Xing;WANG Jianta;WANG Cong;TANG Lei(College of Pharmacy,Guizhou Medical University,Guiyang 550025,Guihzou,China;Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guiyang 550004,Guihzou,China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550025 [2]贵州省化学合成药物研发利用工程技术研究中心,贵州贵阳550004

出　　处：《贵州医科大学学报》2023年第9期1020-1025,共6页Journal of Guizhou Medical University

基　　金：2023年度贵州省卫生健康委科学技术基金项目(gzwkj2023-232);化学药仿创技术应用国家地方联合工程技术研究中心(2019);贵州省常见重大慢性疾病发病机制及药物开发应用创新基地(黔科中引地〔2021〕4029)。

摘　　要：目的探讨黄酮类衍生物的合成及对黄嘌呤氧化酶(XO)活性的影响。方法以2,4,6-三羟基苯乙酮、间苯三酚和对羟基苯丙酸分别为原料,合成二氢黄酮、黄酮和二氢异黄酮类化合物;非布索坦作为阳性对照,目标化合物a~c作为实验组,以25μmol/L为起始浓度,采用尿酸(UA)法检测XO的活性,采用分子对接预测化合物与靶蛋白的结合方式。结果设计合成了化合物a~c共3个黄酮类化合物,结构经氢核磁共振(^(1)H NMR)及高分辨质谱(HRMS)确认;目标化合物a~c于25、50、100及200μmol/L浓度下均有XO抑制活性,分子对接表明化合物b与XO受体有多个氨基酸结合位点。结论设计合成的黄酮类化合物b对XO具有较好的抑制活性。Objective To explore the synthesis of flavonoids derivatives and their effect on the activity of xanthine oxidase(XO).Methods Dihydroflavonoids,flavones and dihydroislavones were synthesized from 2,4,6-trihydroxyacetenone,resorcinol and p-hydroxyphenylpropyloic acid,respectively.Febuxostan was used as a positive control,and the target compounds a-c were used as the experimental group.With 25μmol/L is the starting concentration,the activity of XO was detected by the uric acid(UA)method,and the binding method was predicted to the target protein by molecular docking.Results A total of three flavonoids from a-c were designed and synthesized,and the structure was confirmed by hydrogen nuclear magnetic resonance(^(1)H NMR)and high resolution mass spectrometry(HRMS).The target compounds a-c showed XO inhibitory activity at concentrations of 25,50,100,and 200μmol/L.Molecular docking indicates that compound b has multiple amino acid binding sites with the XO receptor.Conclusion The designed and synthesized flavonoids b have a better inhibitory activity against XO.

关 键 词：黄酮类 非布索坦 分子对接模拟 黄嘌呤氧化酶抑制剂 合成 生物活性 

分 类 号：R914.5[医药卫生—药物化学]