紫杉醇类似物的电子结构与抗癌活性关系的研究(Ⅰ)  

STUDY ON THE RELATIONSHIPS BETWEEN THE ELECTRONIC STRUCTURE AND ANTIMITOTIC ACTIVITY OF PACLITAXEL ANALOGUES(Ⅰ)

作　　者：徐志广[1] 许旋[1] 李卫华[1] 罗一帆[2] 

机构地区：[1]华南师范大学化学系,广东广州510631 [2]中山医科大学天然药物研究室,广东广州510089

出　　处：《华南师范大学学报（自然科学版）》2001年第3期97-102,共6页Journal of South China Normal University(Natural Science Edition)

摘　　要：应用MM3分子力学方法对R6=H的13个紫杉醇类似物进行几何优化,并采用MNDO法计算了化合物的电子结构,应用回归分析、神经网络等方法寻找其量化指数与抗癌活性的关系.结果表明,R2取代基、2-OBz中苯甲酰基(Bz)的碳氧原子的净电荷之和∑QBz、核-核排斥能Ep对活性影响较大.并得到显著性较好的QSAR:ID50(A)/ID50(T)(act)=71.20535+155.35016∑QBz,表明随着∑QBz减小,ID50(A)/ID50(T)值将减小,而化合物活性将增大.神经网络(BP网络)算法的结果表明,神经网络计算值R=O.992,神经网络的结果可精确地预测化合物的抗癌活性.To analyze the QSAR of 13 paclitaxel analogues (for R6 = H), the MM3 geometry optimization and MNDO quantum chemical indexes have been performed. It is concluded that the change of R2 group, the sum of net charge of carbon and oxygen atoms of Bz in 2 - OBz ΣQBz, and the energy of core - core interaction Ep, affect the activity significantly. A significant quantitative relationship between electronic structure and antimitotic activity of paclitaxel analogues was obtained as follows: ID50(A)/ID50(T)(act) = 71.20535 + 155.35016ΣQBz . The QSAR reveals that the values of ID50 (A)/ID50(T) (act) are decreased , and the activities are increased as the decrease of Σ QBz. The superior predictions were obtained, by neural network in the research.

关 键 词：紫杉醇类似物 MM3 MNDO QSAR 神经网络 电子结构 抗癌活性 量化指数 

分 类 号：R979.1[医药卫生—药品] R917[医药卫生—药学]