Department of Pharmacognosy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
Interdisciplinary Center for Nanotoxicity, Department of Chemistry, Physics and Atmospheric Sciences, Jackson State University, 1400 J. R. Lynch str., Jackson, MS 39217, USA.
Molecules. 2020 Jul 7;25(13):3088. doi: 10.3390/molecules25133088.
Phenolic acids are naturally occurring compounds that are known for their antioxidant and antiradical activity. We present experimental and theoretical studies on the antioxidant potential of the set of 22 phenolic acids with different models of hydroxylation and methoxylation of aromatic rings. Ferric reducing antioxidant power assay was used to evaluate this property. 2,3-dihydroxybenzoic acid was found to be the strongest antioxidant, while mono hydroxylated and methoxylated structures had the lowest activities. A comprehensive structure-activity investigation with density functional theory methods elucidated the influence of compounds topology, resonance stabilization, and intramolecular hydrogen bonding on the exhibited activity. The key factor was found to be a presence of two or more hydroxyl groups being located in or position to each other. Finally, the quantitative structure-activity relationship approach was used to build a multiple linear regression model describing the dependence of antioxidant activity on structure of compounds, using features exclusively related to their topology. Coefficients of determination for training set and for the test set equaled 0.9918 and 0.9993 respectively, and Q2 value for leave-one-out was 0.9716. In addition, the presented model was used to predict activities of phenolic acids that haven't been tested here experimentally.
酚酸是一种天然存在的化合物，以其抗氧化和抗自由基活性而闻名。我们用不同的芳环羟化和甲氧基化模型对 22 种酚酸的抗氧化潜力进行了实验和理论研究。采用铁还原抗氧化能力测定法来评估这种特性。研究发现，2,3-二羟基苯甲酸是最强的抗氧化剂，而单羟基化和甲氧基化结构的活性最低。用密度泛函理论方法进行了全面的结构-活性研究，阐明了化合物拓扑、共振稳定化和分子内氢键对所表现出的活性的影响。关键因素是存在两个或更多的羟基，彼此位于邻位或对位。最后，使用定量结构-活性关系方法构建了一个多元线性回归模型，用于描述抗氧化活性与化合物结构之间的关系，该模型仅使用与其拓扑结构相关的特征。训练集和测试集的决定系数分别为 0.9918 和 0.9993，留一法的 Q2 值为 0.9716。此外，该模型还用于预测未在此实验中测试过的酚酸的活性。
