摘要
利用密度泛函理论(DFT)在杂化泛函B3LYP和基组6-311G(d,p)水平下对7,10-位双取代喜树碱衍生物(CPTs)进行了构型优化,计算出分子的电子结构描述符,利用Chemoffice 8.0软件计算出几个相关的物化描述符;采用逐步多元回归法对该组化合物的抗癌活性与分子描述符之间建立了定量结构-活性关系(QSAR)模型。所建最佳三参数QSAR模型的复相关系数R=0.951;用留一法(leave-one-out,LOO)进行交互检验,得到交互检验系数RCV2=0.778。结果表明,所得QSAR模型具有良好的预测能力,而且影响药物活性的主要因素有化合物分子的结构、最高占据和最低空分子轨道能量差及13-位碳原子的净电荷。
The geometrical structures of 7,10-substituted camptothecin derivatives（ CPTs） were optimized and the corresponding e-lectronic structure descriptors were calculated using DFT/B3LYP procedure at 6-311G（d,p）level. Several correlated physiochemi-cal descriptors of the compounds were calculated using the program Chemoffice 8. 0. A reasonable QSAR（ quantitative structure-ac-tivity relationship）equation for predicting the anticancer activity of the 7,10-CPTs was achieved with a quite high correlation coeffi-cient（R=0. 951）by a step multiple regression. The performance of the models were tested through cross-validation by the leave-one-out procedure（ LOO） and the complex correlation coefficient was RCV 2=0. 778. The results show that not only those QSAR models have good predictive ability, but also molecular complexity, the energy difference △ELH between the lowest unoccupied and the highest occupied molecular orbitals,and net charges of 13-carbon atom are the main factors affecting the antitumor activity of the camptothecin derivatives.
出处
《化学研究与应用》
CAS
CSCD
北大核心
2014年第8期1339-1342,共4页
Chemical Research and Application
基金
山西省自然科学基金(2007011025)
关键词
喜树碱衍生物
抗癌活性
定量构效关系
密度泛函理论
quantitative structure-activity relationship （ QSAR ）
camptothecin （CPT）
anticancer drug
density functional theory（DFT）
