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

筛选出抗H1N1活性好和细胞毒性低的化合物,初步探明结构与抗H1N1活性之间的关系。采用MTT法,以体外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。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IC50值分别为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%)。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。研究结果可为多酚类抗病毒药物的筛选、合理设计,结构修饰提供指导。

To screen out the compounds with good anti-H1N1 activity and low cytotoxicity and preliminarily identify the relationship between structure and antiviral activity.cells.The antivirual activities and cytotoxicity assay of these compounds were tested at a cellular level.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%.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 C2-C3 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.