苦参黄酮抑制血管新生活性成分的虚拟筛选.docVIP

苦参黄酮抑制血管新生活性成分的虚拟筛选 　　[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VEGFa，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 25（DS25） 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。 　　[关键词]苦参黄酮； 抗血管新生； 分子对接； 虚拟筛选 　　[Abstract]Angiogenesis is a dynamic， multistep 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 antiangiogenesis flavonoids from the roots of S flavescens One handred and twentysix flavonoids selected from S flavescens were screened in the docking ligand database with six targets（VEGFa，TEK，KDR，Flt1，FGFR1 and FGFR2） as the receptors In addition， the smallmolecule approved drugs of targets from DrugBank database were set as a reference with minimum score of each target′s approved drugs as threshold The LibDock module in Discovery Studio 25 （DS25） 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 antiangiogenesis was preliminarily revealed， which provided a new method for the development of angiogenesis inhibitor drugs 　　[Key words]flavonoids from Sophora flavescens； antiangiogenesis； molecular docking； virtual screening 　　血管新生是一??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[1]，肿瘤、糖尿病、动脉粥样硬化等重大疾病的病理环节都与血管新生有关[24]，故研究血管新生抑制剂具有重要意义。血管新生主要过程包括血管基底膜降解，血管内皮细胞的激活、增殖、迁移，以芽生方式在原有血管基础上重构新的血管和血管网，这一过程主要由可溶性血管生成刺激因子诱导[510]，如VEGF，KDR，VEGF可增加血管通透性，其受体KDR是抗VEGF受体疗法的一种主要靶点，为早期成血管细胞发育所必需；FLT1，使成血管细胞形成血