紫杉醇类似物定量构效关系(QSAR)的研究  

The QSAR research of paclitaxel analogues

作　　者：高峰[1] 李燕[1] 王永华[2] 张述伟[1] 

机构地区：[1]大连理工大学化工学院化学工艺教研室,辽宁大连116012 [2]大连水产学院生命科学与技术学院,辽宁大连116023

出　　处：《计算机与应用化学》2010年第3期329-336,共8页Computers and Applied Chemistry

基　　金：国家自然科学基金(No.10801025);大连理工大学青年教师培养基金资助课题(No.1000-893231);大连理工大学博士科研启动基金资助课题(No.1000-893361)

摘　　要：紫杉醇是从紫杉或称红豆杉中提取的1种天然抗癌物质,具有独特的抗癌机理。由于紫杉醇的种种限制,开发具有更高抗癌活性的紫杉醇类似物药物具有广阔的前景。本文选用36个结构多样的紫杉醇类似物分子作为数据集,随机选取其中28个作为训练集,其它为检验集,采用多元线性回归(MLR)法及主成分回归分析(PCA)法分析每个化合物的197个分子参数,分别建立定量构效关系的最优预测模型。并用检验集检验所建模型的预测能力。结果表明:多元线性回归分析法所建模型与主成分回归所建模型相比,发现逐步筛选法为最优建模方法。该方法所建模型统计结果良好(R^2=0.846,SEE=1.060),应用于检验集时,结果也比较满意(R^2=0.841,SEP=1.071),模型的可靠性和预测性较强。建模和确定主要影响因素有助于指导筛选和研发新型类紫杉醇药物。The paclitaxel is a natural anti-cancer material extracted from yews, having the unique anti-cancer mechanism. Because of many reasons, developing higher anti-cancer drugs has broader prospects. We built a dataset composed of 36 paclitaxel analogues with diversiform structures, 28 compounds served as training set and the rest as test set, regressed the 197 molecular indices by multivariate linear regression and principal component regression analysis methods and finally got the best predictable mathematic models of their own. From the analysis of the model, stepwise regression analysis was found to be the optimal regression method compared with other multivariate linear regressions and principal component regression analysis. The model built on this method showed satisfactory statistical results （R2 = 0. 846, SEE = 1. 060 ）, whose proper predictability was validated by the independent test set （ R2 = 0. 841, SEP = 1. 071 ）. The key descriptors were identified, which are valuable and helpful for further researching and development of new paclitaxel analogues drugs.

关 键 词：紫杉醇类似物 分子参数 多元线性回归分析 主成分回归 

分 类 号：O641.12[理学—物理化学] Q74[理学—化学]