苦参黄酮抑制血管新生活性成分的虚拟筛选  

Virtual screening of anti-angiogenesis flavonoids from Sophora flavescens

作　　者：陈锡欣[1] 刘怡[2] 黄荣[1] 赵林林[1] 陈磊[1,3,4] 王淑美[1,3,4] 

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]南方医科大学中医药学院,广东广州510515 [3]国家中医药管理局中药数字化质量评价技术重点研究室,广东广州510006 [4]广东高校中药质量工程技术研究中心,广东广州510006

出　　处：《中国中药杂志》2017年第6期1140-1145,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81303193;81403063;81673556)

摘　　要：血管新生是一个动态的、多步骤的过程,现在已知大约70种疾病与血管新生紊乱相关。作者前期研究及文献报道均表明苦参黄酮类成分有明显抑制血管新生的作用,但其药效物质基础和作用机制尚未明确。该研究应用分子对接技术虚拟筛选苦参黄酮抑制血管新生的药效物质,搜集现已分离鉴定的126个苦参黄酮类化合物组成配体数据库,选择VEGF-a,TEK,KDR等6个与血管新生密切相关的靶点组成受体数据库,以DrugBank中对各靶点有抑制作用并已上市的小分子药物为参照,设定各靶点对应的已上市小分子药物最低打分为阈值,应用Discovery Studio 2.5(DS2.5)软件的LibDock模块进行分子对接,虚拟筛选出打分高于阈值且排名前10%的化合物共37个。对比分析了原配体、已上市药物和苦参黄酮作用于各靶点的主要活性位点,初步揭示了苦参黄酮抑制血管新生的作用机制,为研发血管新生抑制剂类药物提供了一定的参考。Angiogenesis is a dynamic, multi-step process. It is known that about 70 diseases are related to angiogenesis. Both the experimental and the literature reports showed that Sophora flavescens inhibit angiogenesis significantly, but the material basis and the mechanism of action have not been clear. In this study, molecular docking was used for screening of anti-angiogenesis flavonoids from the roots of S. flavescens. One handred and twenty-six flavonoids selected from S. flavescens were screened in the docking ligand database with six targets（ VEGF-a, TEK, KDR, Fhl, FGFR1 and FGFR2） as the receptors. In addition, the small-molecule approved drugs of targets from DrugBank database were set as a reference with minimum score of each target＇s approved drugs as threshold. The Lib- Dock module in Discovery Studio 2. 5 （DS2. 5 ） software was applied to screen the compounds. As a result, 37 compounds were screened out that their scores were higher than the minimum score of approved drugs as well as being in the top of 10%. At last the mechanism of flavonoids anti-angiogenesis was preliminarily revealed, which provided a new method for the development of angiogenesis inhibitor drugs.

关 键 词：苦参黄酮 抗血管新生 分子对接 虚拟筛选 

分 类 号：R284[医药卫生—中药学]