CAJ | 학술논문

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RCV 2=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。
이용밀도범함이론(DFT)재잡화범함B3LYP화기조6-311G(d,p)수평하대7,10-위쌍취대희수감연생물( CPTs)진행료구형우화,계산출분자적전자결구묘술부,이용Chemoffice 8．0연건계산출궤개상관적물화묘술부；채용축보다원회귀법대해조화합물적항암활성여분자묘술부지간건립료정량결구-활성관계( QSAR)모형。소건최가삼삼수QSAR모형적복상관계수R=0．951；용류일법( leave-one-out,LOO)진행교호검험,득도교호검험계수RCV 2=0．778。결과표명,소득QSAR모형구유량호적예측능력,이차영향약물활성적주요인소유화합물분자적결구、최고점거화최저공분자궤도능량차급13-위탄원자적정전하。
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.