摘要
目的探讨四氢异喹啉类生物碱类化合物的结构与其抗肿瘤活性之间的定量构效关系。方法使用计算化学软件Chem3D、SYBYL-X 2.0及逐步回归分析方法进行四氢异喹啉化合物结构的构建、分子的优化、描述符的计算与筛选。运用多元线性回归和偏最小二乘回归分别建立以化合物结构量化参数为自变量,抗肿瘤活性数据(半数抑制浓度IC_(50))的负对数值pIC_(50)为因变量的定量构效关系模型,并对两种模型进行对比分析。结果两种模型均表明脂水分配系数、分子总能量、应变能对化合物抗肿瘤活性有显著影响,且两种模型中自变量对因变量的正负影响关系一致。多元线性回归模型拟合优度R^(2)=0.719,预测相关系数R^(2)pred=0.695>0.5。偏最小二乘回归模型拟合优度为0.675。预测相关系数R^(2)pred=0.524>0.5。结论两种模型对四氢异喹啉类生物碱抗肿瘤活性均具有良好的预测能力,其中多元线性回归略优于偏最小二乘回归。所建模型可为新型四氢异喹啉类生物碱衍生物的设计与合成提供理论上的指导。
Objective To investigate the quantitative structure-activity relationship between the structure of tetrahydroisoquinine alkaloids and their anti-tumor activity.Methods The computational chemistry software Chem3 D,Sybyl-X 2.0 and stepwise regression analysis were used to finish the tetrahydroisoquinoline compound structure construction,molecular optimization,descriptor calculation and screening.Multiple linear regression and partial least squares regression were used to establish quantitative structure-activity relationship models with quantitative parameters of compound structure as independent variables and the negative pair value of anti-tumor activity data(pIC_(50))as dependent variable,and the two models were compared analyzed.Results Both models showed that ClogP,energy and strain energy had significant effects on the anti-tumor activity of the compounds,and the positive and negative effects of independent variables on dependent variables were consistent in the two models.The goodness of fit of the multivariate linear regression model was 0.719,and the prediction correlation coefficient was 0.695>0.5.The goodness of fit of partial least squares regression model was 0.675 and the predicted correlation coefficient was 0.524>0.5.Conclusion Both models have good predictive ability for the anti-tumor activity of tetrahydroisoquinoline alkaloids,multivariate linear regression is slightly better than partial least squares regression.The model can provide theoretical guidance for the design and synthesis of novel tetrahydroisoquinoline alkaloid derivatives.
作者
翟明明
高畅
ZHAI Mingming;GAO Chang(School of Medical Devices,Shenyang Pharmaceutical University,Shenyang 110016,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China)
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2021年第11期1213-1223,共11页
Journal of Shenyang Pharmaceutical University
基金
沈阳药科大学中青年教师事业发展支持计划(ZQN2018022)。
关键词
四氢异喹啉类生物碱
抗肿瘤
定量构效
多元回归分析
偏最小二乘法
tetrahydroisoquinoline
anti-tumor activity
quantitative structure-activity relationship(QSAR)
multiple regression analysis
partial least squares
