摘要
目的建立黄酮类化合物对大鼠心肌细胞抗凋亡率的定量构效关系模型,探讨其抗凋亡作用的微观机制。方法采用半经验量子化学计算法MOPAC-AM1计算黄酮类化合物的量化参数,运用最佳变量子集回归及人工神经网络BP算法建立黄酮类化合物抗凋亡率的QSAR模型。结果最佳二元线性回归模型的交叉验证系数(r2CV)为0.707,非交叉验证的相关系数(r)为0.928;相应BP-QSAR模型的r为0.996,估计标准误差(S)为0.013。结论羟基指数(L)与碳电荷(QC)揭示了影响黄酮类化合物抗凋亡率的本质因素;其中,A、C环上羟基对自由基的链传递起主要阻断作用。
OBJECTIVE To study the quantitative structure-activity relationship（QSAR） between the anti-apoptosis activity and the charge of the carbon atom（QC）,the hydroxyl index（L） of ten natural flavones on the rat cardiocyte,and analyze the microcosmic mechanism of anti-apoptosis action of flavones on the rat cardiocyte.METHODS The quantum chemical parameters of ten natural flavones were calculated by MOPAC-AM1 method.The QSAR models were established with Leaps-and-Bounds regression and the back-propagation algorithm of artificial neural network（BP-ANN）.RESULTS The coefficients of cross-validation（r2CV） and noncross-validation（r） of the optimum linear model between the anti-apoptosis activity and QC,L were 0.707 and 0.928.A satisfied model of 2∶2∶1 network architecture were constructed by the back-propagation algorithm,whose correlation coefficient（r） and the standard error（S） were 0.996 and 0.013.CONCLUSION Using the model mentioned above,the main factors to influence the anti-apoptosis activity can be illustrated by the QC and the L of the flavone molecules.The chain transfer of the free radical is mainly inhibited by the hydroxyls of the A cycle and the C cycle.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2010年第12期952-956,共5页
Chinese Pharmaceutical Journal
基金
国家"973"计划项目(2004CB719903)
国家自然科学基金资助项目(20776149)
环境模拟与污染控制国家重点联合实验室基金(KJ2007001)
徐州工程学院培育课题(XKY2008313
XKY2009208)
关键词
黄酮类化合物
抗凋亡活性
羟基指数
碳电荷
定量构效关系
flavones
anti-apoptosis activity
hydroxyl index
charge of the carbon atom
quantitative structure-activity relationship
