混合线性模型在黄酮类化合物QSAR研究中的应用

Application of Mixed Linear Model in QSAR Study of Flavonoids

目的:采用混合线性模型(MLM)构造定量结构-活性关系(QSAR)模型阐明黄酮类化合物与其抗氧化活性之间的构效关系,从而对该类先导化合物的设计提供依据。方法:从PubMed数据库中检索并收集黄酮类化合物对1,1-二苯基-2-三硝基苯肼(DPPH)的半抑制浓度(IC_(50))的文献,并根据其分子结构特征与IC_(50)值建立数据库。通过MLM构造初始QSAR模型,应用五折交叉验证法进行模型优化,最终得到预测模型。结果:黄酮类化合物的抗氧化活性与A环的邻二酚羟基数目(X_(1))和B环的酚羟基数目(X_(2))呈正相关,与B环的间二酚羟基数目(X_(3))呈负相关。优化后的模型为:IC_(50)=137.56-65.86X_(1)-53.92X_(2)+70.85X_(3)。结论:采用MLM进行QSAR研究能较好地预测黄酮类化合物的抗氧化活性,为抗氧化药物的设计提供参考。

Objective:To elucidate the structure-activity relationship between flavonoids and their antioxidant activities by constructing a quantitative structure-activity relationship(QSAR)model using mixed linear model(MLM),hence to provide the basis for the design of these lead compounds.Methods:Literature that reported the half maximal inhibitory concentration(IC_(50))of flavonoids against DPPH was retrieved and collected from the PubMed database,and a database was established based on their molecular structure characteristics and IC_(50) values.The initial QSAR model was constructed through MLM,the five-fold cross-validation method was applied to optimize the model,and finally the prediction model was obtained.Results:The antioxidant activity of flavonoid compounds was positively correlated with the numbers of ortho-phenolic-dihydroxyl in A ring(X_(1))and the numbers of phenolic-hydroxyls in B ring(X_(2)),and negatively correlated with meta-phenolic-dihydroxyl in B ring(X_(3)).The optimized equation was that IC_(50)=137.56-65.86X_(1)-53.92 X_(2)+70.85X_(3).Conclusion:The established QSAR model by MLM could explicitly predict the antioxidant activity of flavonoids,and provide reference for the design of antioxidants.