紫杉醇类似物抗癌活性与分子结构的定量构效关系.pdf

• 318 • 中草药 Chinese Traditional and Herbal Drugs 第 42 卷 第 2 期 2011 年 2 月 紫杉醇类似物抗癌活性与分子结构的定量构效关系 陈 艳，堵锡华 徐州工程学院化学化工学院，江苏 徐州 221008 摘 要：目的 为了寻找新一代紫杉醇类抗癌药物，研究紫杉醇类似物分子结构和抗癌活性（PIDact ）之间的定量构效关系。 方法 基于电性状态拓扑指数和电性距离矢量，应用最佳子集回归的方法建立了 PIDact 值和紫杉醇类似物分子结构的定量结 构–活性相关（QSAR ）模型，并对模型进行了交互检验和外部检验，用 43 个紫杉醇类似物训练集样本构建的 QSAR 模型 预测了外部 10 个检验集的 PIDact 值。结果 所建立模型具有较高的估计相关系数及 LOO （leave-one-out ）检验相关系数。 结论 模型具有良好估计能力与稳定性，训练集模型具有良好预测能力。 关键词：紫杉醇类似物；构效关系；抗癌活性；电性状态拓扑指数；电性距离矢量 中图分类号：R286.91 文献标志码：A 文章编号：0253 - 2670(2011)02 - 0318 - 06 Relationship between anticancer activity and molecular structure of paclitaxel analogues CHEN Yan, DU Xi-hua School of Chemistry and Chemical Engineering, Xuzhou Institute of Technology, Xuzhou 221008, China Abstract: Objective To develop a new generation of anticancer drugs of paclitaxel, the quantitative structure-anticancer activity (PIDact) relationship (QSAR) of paclitaxel analogues was studied. Methods Based on the electrotopological state index and electronegativity distance vector, the QSAR model was developed by Leaps-Bounds regression (best subset, LBR), and was validated using cross and external-validation. PIDact values of ten external validation were predicted by the QSAR model built from the training set with 43 paclitaxel analogues. Results The model had higher calibrated correlation coefficient and LOO (leave-one-out) validated correlation coefficient. Conclusion The model has estimated ability and good stability, and the training set model has good predictive ability. Key words: paclitaxel analogues; structure-effect relationship; anticancer activity; electrotopological state index; electronegativity distance vector 紫杉醇是从红豆杉属植物的树皮中提取出来的 所谓构效关系研究就是建立药物分子结构与实 抗癌药物，其新颖的分子结构、独特的抗癌作用机 验可测的药效学数据相关联的定量构效关系 制和良好的抗癌活性引起了化学和药学工作者的关