天然黄酮类化合物的神经氨酸酶抑制活性评价

Evaluation for inhibitory effects of natural flavonoids on neuraminidases

目的:评价芹菜素等15个不同结构类型的天然黄酮类化合物对流感病毒NA的抑制活性,初步分析其构效关系,并对其中活性较高者进行NA抑制作用的特异性分析。方法:应用荧光测定法进行体外酶活性评价。结果:经检测,发现芹菜素、木犀草素、芹菜苷、木犀草苷、高车前素、黄芩素和山萘酚对流感病毒NA的抑制活性较好,半数抑制浓度(IC50)低于60μmol.L-1;在这7个化合物中,除高车前素对3个物种来源NA的抑制活性差异不显著外,芹菜素、木犀草素、芹菜苷、木犀草苷、黄芩素和山萘酚对流感病毒NA的抑制活性均高于其对霍乱弧菌、大鼠肝脏NA的抑制活性(P<0.05)。结论:芹菜素等15个黄酮类化合物对流感病毒NA均具有一定的抑制作用,其中芹菜素、木犀草素、芹菜苷、木犀草苷、高车前素、黄芩素和山萘酚活性最好,初步SAR分析提示,黄酮类化合物C2和C3位之间的双键,C4位上的C=O对于其流感病毒NA抑制活性是必需的,A环上C5位,C7位和B环上C4位上的-OH对于NA抑制活性非常重要。这15个化合物中,芹菜素、木犀草素、芹菜苷、木犀草苷、黄芩素和山萘酚对流感病毒NA的抑制作用具有特异性。

Objective： To investigate the inhibitory effects of 15 different natural flavonoids on neuraminidases （NAs） from influenza virus, and to evaluate the specificity of their inhibitory effects on NAs and analyze the structure-activity relationship （ SAR）. Methods ： Fluorometrie assay was used to test the activities of NAs in vitro. Results： All the 15 flavonoids possessed inhibitory activities against influenza virus NAs. Apigenin, luteolin, apiin, galuteolin, dinatin, scutellarin and kaempferol were the best ; their IC50 values were lower than 60 μmol·L^-1. The effects of apigenin, luteolin, apiin, galuteolin, scutellarin and kaempferol on influenza virus NAs were much more potent than their effects on NAs from vibrio cholerae and rat liver, while dinatin had similar effects on these NAs. Conclusion： All the 15 flavonoids inhibit influenza virus NAs, and effects of apigenin, luteolin, apiin, ga- luteolin, dinatin, scutellarin and kaempferol are the most potent. The SAR analysis of flavonoids＇ effects on influenza virus NAs reveals that for inhibitory potency, C4 = O and C2 = C3 functionalities are essential, and the 5-OH, 7- OH and 4＇-OH are important. Apigenin, luteolin, apiin, galuteolin, scutellarin and kaempferol have shown the specificity of inhibitory effects on influenza virus NAs. These findings provide important information for the exploitation and utilization of these flavonoids.