齐墩果烷及熊果烷型五环三萜抗肝损伤作用及其构效关系研究

Reasearch on Urosane-type and Oleane-type Triterpenoids with Liver Protective Activity and Their Quantitative Structure-Activity Relationship

研究3种广东地区习用中药中32个齐墩果烷及熊果烷型五环三萜化合物对肝损伤的保护作用及其构效关系。采用体外氧化肝损伤模型,测定分离得到的五环三萜化合物对损伤肝细胞的保护作用;以化合物的分子结构参数与损伤肝细胞保护作用构建比较分子场分析(CoMFA)模型,并研究其构效关系。建立的CoMFA模型证实上述化合物的结构参数与其对氧化肝损伤细胞保护活性存在明显的相关性(模型的相关系数γ2为0.976),且有良好的预测能力(交叉验证相关系数q2为0.719),同时使用"留一法"证实模型的稳定性和可靠性。熊果烷型三萜较齐敦果烷型三萜的保肝活性明显增强,根据获得的模型的三维等势图,前者在3、19、20、23和24等5个取代位置添加带负电荷的基团,如-OH,则使化合物的保肝活性明显提高;如在这些位置引入疏水性较强的基团,如-CH3等,则可能使化合物的保肝活性降低。应用所构建的CoMFA模型预测化合物的活性与实测值接近,表明所建模型具有良好的预测性。

The liver protective activity of 32 triterpenoids with their quantitative structure-activity relationship was investigated using our previously developed in vitro method.The Comparative Molecular Field Analysis （CoMFA） approach was used to probe the quantitative relationships between the triterpenoids＇ molecular structural descriptors and their liver protective activities.A reliable CoMFA model with the combined electrostatic and hydrophobic fields was derived with the regression coefficient γ2 of 0.976 and the cross-validation regression coefficient q2 of 0.719,separately,which was capable of elucidating the quantitative relationship between the 3D structural descriptors of the triterpenoids and their bioactivities.Comparing with triterpenoids,the larger negative charge of triterpenoids significantly improved the biologically inhibitory ability.Based on the core structure of the latter,either electropositive substituents or hydrophobic groups at the 3,19,20,23 and 24 ring positions can enhance the liver protective activity according to the CoMFA contour maps.