基于醛固酮拮抗活性和专利检索的降压中药组方设计  

Method of traditional Chinese medicine formula design based on 3D-database pharmacophore search and patent retrieval

作　　者：贺昱甦 孙志一 张燕玲[1] 

机构地区：[1]北京中医药大学中药学院,北京100102 [2]北京东方灵盾科技有限公司,北京100191

出　　处：《中国中药杂志》2014年第22期4411-4417,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81173522);国家"重大新药创制"科技重大专项(2011ZX09401-028)

摘　　要：该文从降压靶标醛固酮受体出发,构建其拮抗剂药效团模型,搜索中药化学数据库(traditional Chinese medicines database,TCMD),寻找潜在的中药醛固酮受体拮抗剂,并结合方剂专利检索结果,设计降压中药组方。其中,药效团模型以对人源醛固酮受体具有拮抗活性的33个化合物为研究对象,利用3D-QSAR pharmacophore(Hypogen)模块建立,最优模型由2个氢键受体、3个疏水基团以及4个排除体积组成,预测训练集化合物活性相关系数为0.953 4、测试集相关系数为0.674 8,辨识有效性指数N为2.878、综合评价指数CAI为1.119。采用最优模型对TCMD数据库进行筛选,命中1 700个化学成分,获得86味来源中药材,涉及常用中药24味。由于现有中医经典中未有记载治疗高血压病的用药方案以供参考,故该文利用所得药材在世界传统药物专利数据库(world traditional medicine patent database,WTM)中用于降压的统计结果,针对痰浊中阻型、瘀血阻滞型高血压,探讨了降压组方设计。By using the pharmacophore model of mineralocorticoid receptor antagonists as a starting point,the experiment studies the method of traditional Chinese medicine formula design for anti-hypertensive. Pharmacophore models were generated by 3D-QSAR pharmacophore（ Hypogen） program of the DS3. 5,based on the training set composed of 33 mineralocorticoid receptor antagonists. The best pharmacophore model consisted of two Hydrogen-bond acceptors,three Hydrophobic and four excluded volumes. Its correlation coefficient of training set and test set,N,and CAI value were 0. 953 4,0. 674 8,2. 878,and 1. 119. According to the database screening,1 700 active compounds from 86 source plant were obtained. Because of lacking of available anti-hypertensive medication strategy in traditional theory,this article takes advantage of patent retrieval in world traditional medicine patent database,in order to design drug formula. Finally,two formulae was obtained for antihypertensive.

关 键 词：降压 醛固酮受体拮抗剂 药效团模型 中药化学数据库 世界传统药物专利数据库 中药组方 

分 类 号：R289[医药卫生—方剂学]