苯甲酰脲类抗肿瘤β微管蛋白抑制剂药效团模型的构建及应用.pdfVIP

462 药学学报 Acta Pharmaceutica Sinica 2010, 45 (4) : 462466 苯甲酰脲类抗肿瘤 微管蛋白抑制剂药效团模型的构建与应用 高丽梅, 张胜华, 易 红, 蒋建东, 宋丹青* ( 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) 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 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 微管蛋白抑制剂。 关键词: 计算机辅助药物设计; 微管蛋白抑制剂; 药效团模型 中图分类号: R916 文献标识码:A 文章编号: 05 13-4870 (2010) 04-0462-05 Construction and application of pharmacophore model of benzoylurea derivatives as -tubulin inhibitors * GAO Li-mei, ZHANG Sheng-hua, YI Hong, JIANG Jian-dong, SONG Dan-qing (Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences Beij ing Union Medical College, Beij ing 100050, China) Abstract: Ten pharmacophore models of -tubulin inhibitors were established from the training set of seventeen -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 -tubulin inhibitors and can be further used to identify structurally diverse compounds with higher activity. Key words: CADD; -tubulin inhibitor; pharmacophore model 微管蛋白 (tubulin) 是细胞骨架的重要组成部 苯甲酰脲类化合物是作者发现的一类结构新颖、 [5 7] 分, 主要由α 和 两种微管蛋白亚单位组成,