天然黄酮类化合物对大鼠心肌细胞抗凋亡作用的微观机制及构效关系研究

 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（r 2_CV）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(Q_C)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。

Investigation of the Microcosmic Mechanism and the Quantitative Structure-activity Relationship of Natural Flavones on the Anti-apoptosis Activity in Rat Cardiocyte

OBJECTIVE To study the quantitative structure-activity relationship (QSAR) between the anti-apoptosis activity and the charge of the carbon atom (Q_C)， 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(r2_CV) and noncross-validation(r) of the optimum linear model between the anti-apoptosis activity and Q_C， 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 Q_C 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.