天然咖啡酰基奎宁酸类化合物抗RSV活性及其构效关系研究  

Study on Anti-RSV Activities and QSAR of Natural Caffeoylquinic Acid Derivates

作　　者：夏超[1] 李满妹[1] 李药兰[1] 吴霞[2] 

机构地区：[1]暨南大学中药及天然药物研究所,广东广州510632 [2]广东药学院中心实验室,广东广州510006

出　　处：《中药材》2016年第2期383-388,共6页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金(81202429;81473114);广东省自然科学基金重点项目(S2013020012864)

摘　　要：目的:研究天然来源的咖啡酰基奎宁酸类化合物体外抗呼吸道合胞病毒(Respiratory Syncytial Virus,RSV)的活性及其构效关系。方法:采用细胞病变(cytopathic effect,CPE)法对咖啡酰基奎宁酸类化合物抗RSV体外活性进行筛选,MTT法检测化合物对HEp-2细胞的细胞毒性,通过3D-QSAR(three-dimensional quantitative structureactivity relationship)模型分析其构效关系。结果:CPE结果显示咖啡酰基奎宁酸类化合物均表现出较好的抗RSV作用,其中活性最好的4,5-双咖啡酰基奎宁酸甲酯(CQA-4)的IC_(50)=2.5μmol/L,选择性指数SI>153.8,远远优于阳性对照药物利巴韦林(IC_(50)=8.3μmol/L,SI>20);3D-QSAR分析结果显示,咖啡酰基为咖啡酰基奎宁酸衍生物抗RSV的活性基团。结论:天然来源的咖啡酰基奎宁酸类衍生物均具有抗RSV活性,其中双咖啡酰基奎宁酸类化合物活性最好。构效关系研究表明,该类化合物抗RSV活性受其构型和取代基的影响很大。Objective：To study the inhibitory effects of natural caffeoylquinic acid derivates against respiratory syncytial virus （RSV） in vitro and their quantitative structure-activity relationship. Methods：The anti-RSV activities of caffeoylquinic acid derivates were detected by cytopathic effect （CPE） method, MTT assay was adopted to evaluate the cytotoxicities of caffeoylquinic acid derivates and a three-dimensional quantitative structure-activity relationship （3D-QSAR）model was built. Results：The caffeoylquinic acid deri- rates showed different levels of anti-RSV activity. 4,5-d-CQAME（CQA-4）was the most effective anti-RSV compound with IC50 of 2. 5 μmol/L, and the SI was greater than 153.8. Its effect was much better than the positive control drug ribavirin with the IC50 of 8.3 μ moL/ L,and SI 〉 20,respectively. The result of 3D-QSAR study showed that eaffeoyl group was important for the anti-RSV activity. Conclu- sion：Natural caffeoylquinic acid derivates exhibit anti-RSV activity and dicaffeoylquinic derivates are the most effective anti-RSV com- pounds. Both configuration and substituent groups have a great influence on the anti-RSV activity.

关 键 词：咖啡酰基奎宁酸衍生物 抗RSV 构效关系 

分 类 号：R285.5[医药卫生—中药学]