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

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.