苯甲酰脲类抗肿瘤β微管蛋白抑制剂药效团模型的构建与应用  

Construction and application of pharmacophore model of benzoylurea derivatives as β-tubulin inhibitors

作　　者：高丽梅[1] 张胜华[1] 易红[1] 蒋建东[1] 宋丹青[1] 

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050

出　　处：《药学学报》2010年第4期462-466,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30371673);“重大新药创制”科技重大专项资助项目(2009ZX09301-003)

摘　　要：采用Catalyst软件包,选择抗急性淋巴白血病细胞系活性相差较大的2种结构类型的17个苯甲酰脲类β微管蛋白抑制剂化合物作为训练集,经构象分析,构建出最佳药效团模型,该模型含有2个疏水中心(HP)和2个氢键受体(HBA),具有良好的活性预测能力(RMS=0.43,Correl=0.98,Weight=2.06,Config=15.97),有利于设计和改造具有新型结构的β微管蛋白抑制剂。Ten pharmacophore models of β-tubulin inhibitors were established from the training set of seventeen β-tubulin inhibitors （two categories） with comformer analysis by using the Catalyst software. The optimal pharmacophore model with two hydrophobic units and two hydrogen bond acceptor units were confirmed （RMS = 0.43,Correl = 0.98,Weight = 2.06,Config = 15.97）. This pharmacophore model is able to predict the activity of known β-tubulin inhibitors and can be further used to identify structurally diverse compounds with higher activity.

关 键 词：计算机辅助药物设计 β微管蛋白抑制剂 药效团模型 

分 类 号：R916[医药卫生—药学]