摘要
抗血栓是预防和治疗心血管疾病的有效方法之一。基于传统中医理论、作者前期研究和相关文献,发现鱼腥草中生物碱类成分具有潜在的抗血栓活性,但是其药效物质基础和作用机制尚未明确。该研究采用分子对接技术虚拟筛选鱼腥草生物碱抗血栓的药效物质,搜集现已经从鱼腥草中报道的70个生物碱类化合物组成配体化合物库,选择P2Y1,P2Y12,凝血因子FⅪa,凝血因子FⅩa,PAR1,凝血酶等10个与血栓形成密切相关且具有已知晶体结构的靶蛋白作为受体数据库,以Drug Bank中对各靶蛋白有抑制作用并已上市或者即将上市的小分子药物为阳性对照化合物,设定各靶蛋白对应的已上市小分子药物最低打分(S)为阈值,应用Molecular Operating Environment软件(MOE,version 2016)的Dock功能进行分子对接,虚拟筛选出对接评分(S)低于阈值的化合物。对比分析了原配体、已上市药物和鱼腥草生物碱作用于各靶蛋白的主要活性位点,初步揭示了鱼腥草抗血栓活性的作用机制,为抗血栓类药物的研发提供了一定的参考。
Antithrombus is one of the effective methods to prevent and treat cardiovascular diseases.Based on the theory of traditional Chinese medicine,the author’s previous research and relevant literature,it was found that the alkaloids in Houttuynia cordata has potential antithrombotic effect.However,the pharmacological substance basis and antithrombotic mechanism of H.cordata have not been clarified.In this study,molecular docking was used for virtual screening of antithrombotic alkaloids from H.cordata.Seventy alkaloids selected from H.cordata were screened in the docking ligand data-base with teen thrombosis targets with known crystal structures as the receptors.In addition,the small-molecule approved or to be approved drugs of targets from Drug Bank database were set as a positive reference with minimum score(S value)of each target’s approved or to be approved drugs as threshold.The Dock module in Molecular Operating Environment(Version 2016)software was applied to screen the potential active compounds which their scores(S value)were lower than the minimum score of reference.At last the mechanism of antithrombotic effect was preliminarily revealed by compared the main active sites of the test alkaloids with original ligands and references.This study provided some useful information to development of antithrombus drugs.
作者
蒋跃平
陈章义
刘敏
刘海涛
刘韶
JIANG Yue-ping;CHEN Zhang-yi;LIU Min;LIU Hai-tao;LIU Shao(Department of Pharmacy,Xiangya Hospital,Central South University,Changsha 410008,China;Institute of Hospital Pharmacy,Central South University,Changsha 410008,China;School of Pharmacy,Hubei University of Science and Technology,Xianning 437100,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2019年第8期1623-1634,共12页
China Journal of Chinese Materia Medica
基金
湖南省自然科学基金项目(2017JJ3498)
湖南省中医药科研计划项目(201991)
关键词
鱼腥草
抗血栓
生物碱
分子对接
虚拟筛选
Houttuynia cordata
antithrombus
alkaloids
molecular docking
virtual screening
作者简介
通信作者:刘韶,博士,主任药师,主要从事中药化学成分及分析方法的研究,Tel:(0731)84327454,E-mail:liushao999@csu.edu.cn;蒋跃平,博士,主管药师,主要从事天然药物化学及中药分析的研究,E-mail:jiangyueping@csu.edu.cn
