基于药效团模型从中草药数据库中搜索gpIIb／IIIa受体抑制剂  

Discovery of Inhibitors for gpIIb/Ⅲa Receptor from Chinese Herbal Drugs Database by Pharmacophore-Based Virtual Searching

作　　者：李旭东[1] 徐筱杰[1] 胡娟[2] 

机构地区：[1]北京大学化学与分子工程学院,北京100871 [2]福建中医学院,福州350108

出　　处：《物理化学学报》2008年第2期307-312,共6页Acta Physico-Chimica Sinica

基　　金：国家自然科学基金(20375002,90612015);陈可冀中西医结合发展基金(CKJ20060004);福建省卫生厅中医药研究项目(wzy0607)资助

摘　　要：选择20个3,4-二氢-1(1H)-异喹啉酮类gpIIb/IIIa受体抑制剂作为训练集,利用Catalyst软件包建立了gpIIb/IIIa受体抑制剂三维药效团模型.探讨了药效团作用模式.并通过建立的可靠性最佳的药效团模型(线性回归系数r=0.7715),从中草药数据库中虚拟筛选了gpIIb/IIIa受体抑制剂,通过实验活性测定得到了8个抑制ADP活化全血血小板聚集的IC50从40到100μmol·L-1的化合物,进一步证明了所建药效团模型的有效性.3D pharmacophore model was characterized using a training set of gplIb/IIIa inhibitors which consisted of 20 3,4-dihydro-l（1H）-isoquinolinone-based antagonists by the Catalyst program. The best models （linear r=0.7715） were used as database search queries to identify active compounds for glycoprotein IIb/IIIa receptor from the Chinese herbal drugs database （CHDD） and eight active compounds were found by further activity-determined experiment. The validity of the pharmocophore model was proved further by the experimental results.

关 键 词：药效团模型 GPIIB/IIIA 中草药数据库 

分 类 号：R285[医药卫生—中药学]