儿茶素及其类似物体外抗H1N1流感病毒活性及其构效关系的研究  

In Vitro Antiviral Activity of Catechins and Their Analogs Against H1N1 and Their Structure–activity Relationship

作　　者：雷志伟 林艺璐 李露露 郭灿[1] LEI Zhi-wei;LIN Yi-Lu;LI Lu-lu;GUO Can(Tea Reasearch Institute,Guizhou Academy of Agricultural Science,Guiyang,Guizhou 550006,China;School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,Guangdong 510515,China.)

机构地区：[1]贵州省农业科学院茶叶研究所,贵州贵阳550006 [2]南方医科大学药学院,广东广州510515

出　　处：《贵州茶叶》2020年第1期20-23,共4页Journal of Guizhou Tea

基　　金：贵州省自然科学基金([2016]1145);贵州省联合基金([2015]7065)。

摘　　要：目的:筛选出抗H1N1活性好,细胞毒性低的化合物,初步探明结构与抗病毒活性之间的关系。方法:采用MTT法,体外以MDCK为研究对象,测试多酚化合物抗H1N1病毒活性和MDCK细胞毒性。结果:山奈酚、异甘草素、芹菜素、异鼠李素对H1N1流感假病毒A/WSN/3的抑制IC50分别为7.55±0.87,4.47±0.93,4.03±0.80和4.73±0.90μmol/L,其中异鼠李素选择性指数SI最高,大于67.6;构效研究表明,在50μmol/L时,抗流感病毒活性:芹菜素(100%)优于白杨素(54.29%)、芹菜素(100%)优于木犀草素(63.27%)、山奈酚(100%)优于槲皮素(59.29%)。结论:异鼠李素可为抗H1N1提供结构基础;平面刚性结构抗病毒活性优于柔性结构抗病毒活性;C环C2-C3之间的双键与B环C4’的羟基在抗病毒活性中起关键性作用,但是并非B环的羟基越多越好,这些结果有望为多酚类抗病毒药物的筛选、合理设计,结构修饰提供指导。Objective To screen out the compounds with good anti-H1N1 activity and low cytotoxicity and preliminarily identify the relationship between structure and antiviral activity.cells.Methods The antivirual activities and cytotoxicity assay of these compounds were tested at a cellular level.Results The kaempferol,isoliquiritigenin,apigenin and diosmetin showed potent inhibitory activities against H1N1/A/WSN/3 pseudovirus,and their showed the strongest inhibitory activity with an IC50 value of 7.55±0.87,4.47±0.93,4.03±0.80 and 4.73±0.90μmol/L,respectively.Among them,selectivity index of diosmetin is greater than 67.6%.The structure-activity relationship analysis of these compounds indicated that five polyphenols exhibited inhibitory activity against H1N1 psuedovirus in the trend of apigenin﹥kaempferol﹥luteolin﹥quercetin﹥chrysin with inhibition ratio values in the rangeof 54.29%~100%.Conclusion The analysis of structure-activity relationship showed that the antiviral activity of rigid structure was better than that of flexible structure,and the presence of a C 2-C 3 double bond in the B ring and the hydroxyl group at C4'position played a key role in antiviral activity,but addition of one more hydroxyl in the B ring,such as quercetin and luteolin,causes steric hindrance and disfavors the anti-influenza effect.These results are expected to provide guidance for the screening,reasonable design and structural modification of polyphenols antiviral drugs.

关 键 词：多酚 流感病毒 抗病毒 构效关系 

分 类 号：R28[医药卫生—中药学]