距离比较法构建HMG-CoA还原酶抑制剂药效团  

Build a Pharmacophore Model of HMG-CoA Reductase Inhibitors Using Distance Comparison Method

作　　者：崔建华[1] 张燕玲[1] 乔延江[1] 

机构地区：[1]北京中医药大学中药信息工程研究中心,北京100102

出　　处：《世界科学技术-中医药现代化》2008年第5期101-104,共4页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：科技部国家"973"计划(2005CB523401):组分配伍与饮片配伍的相关性研究;负责人:郑虎占;北京市自然基金(7052038):基于药效团的活血化瘀中药筛选方法学研究;负责人:乔延江;北京市重点实验室(JD100260652)清热解毒中药有效成分发现的方法学研究;负责人:乔延江。

摘　　要：目的:考察不同模板分子对距离比较法(DIStance COmparison,DISCO)构建HMG-CoA还原酶抑制剂药效团模型的影响。方法:以MDDR数据库中作用于大鼠肝细胞的13个HMG-CoA还原酶抑制剂为训练集,将活性最高的6个活性分子逐一作为模板分子,用DISCO方法构建的HMG-CoA还原酶抑制剂三维药效团模型和比较分子力场分析法(Comparative Molecular Field Analysis,CoMFA)进行分析。结果:最优HMG-CoA还原酶抑制剂药效团模型包含两个氢键受体和两个疏水中心,其模板分子的刚性和活性适中。结论:利用DISCO方法构建药效团模型时,合理选择模板分子是保证药效团可靠的关键因素之一。Author discussed the impacts of different reference structures on building a pharmacophore model of HMG-CoA reductase inhibitors using DIStance COmparison method （DISCO）. In the study, 13 inhibitors with the pharmacological activity of rat liver cells were obtained from the MDDR database as the training set. Three dimensional pharmacophore models were developed using DISCO. Six high active compounds were selected as reference structures respectively. The results models were evaluated by Compare Molecule Field Analysis （CoMFA）. Analysis results show that most valid 3D pharmacophore models contain two Acceptor atoms, and two Hydrophobics with an intermediate activity and rigidity. It is found that selecting a reasonable reference structure is the key to the validity assurance, when building a phatmacophore model with the approach of DISCO.

关 键 词：HMG—COA还原酶抑制剂 药效团 距离比较法 模板分子 

分 类 号：R914.2[医药卫生—药物化学] R972.6[医药卫生—药学]