Kancheva Vessela D, Dettori Maria Antonietta, Fabbri Davide, Alov Petko, Angelova Silvia E, Slavova-Kazakova Adriana K, Carta Paola, Menshov Valerii A, Yablonskaya Olga I, Trofimov Aleksei V, Tsakovska Ivanka, Saso Luciano
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, "Acad. G. Bonchev" Str., bl.9, 1113 Sofia, Bulgaria.
CNR, Istituto di Chimica Biomolecolare, Traversa La Crucca 3, 07100 Sassari, Italy.
Antioxidants (Basel). 2021 Apr 19;10(4):624. doi: 10.3390/antiox10040624.
Oxidative stress is associated with the increased production of reactive oxygen species or with a significant decrease in the effectiveness of antioxidant enzymes and nonenzymatic defense. The penetration of oxygen and free radicals in the hydrophobic interior of biological membranes initiates radical disintegration of the hydrocarbon "tails" of the lipids. This process is known as "lipid peroxidation", and the accumulation of the oxidation products as peroxides and the aldehydes and acids derived from them are often used as a measure of oxidative stress levels. In total, 40 phenolic antioxidants were selected for a comparative study and analysis of their chain-breaking antioxidant activity, and thus as modulators of oxidative stress. This included natural and natural-like -methoxy and -hydroxy phenols, nine of them newly synthesized. Applied experimental and theoretical methods (bulk lipid autoxidation, chemiluminescence, in silico methods such as density functional theory (DFT) and quantitative structure-activity relationship ((Q)SAR) modeling) were used to clarify their structure-activity relationship. Kinetics of non-inhibited and inhibited lipid oxidation in close connection with inhibitor transformation under oxidative stress is considered. Special attention has been paid to chemical reactions resulting in the initiation of free radicals, a key stage of oxidative stress. Effects of substituents in the side chains and in the phenolic ring of hydroxylated phenols and biphenols, and the concentration were discussed.
氧化应激与活性氧的产生增加或抗氧化酶及非酶防御有效性的显著降低有关。氧气和自由基渗透到生物膜的疏水内部会引发脂质烃“尾部”的自由基分解。这个过程被称为“脂质过氧化”，氧化产物作为过氧化物以及由它们衍生的醛和酸的积累通常被用作氧化应激水平的衡量指标。总共选择了40种酚类抗氧化剂进行比较研究，并分析它们的断链抗氧化活性，从而作为氧化应激的调节剂。这包括天然和类天然的甲氧基和羟基酚，其中9种是新合成的。应用实验和理论方法（大量脂质自氧化、化学发光、密度泛函理论（DFT）和定量构效关系（（Q）SAR）建模等计算机模拟方法）来阐明它们的构效关系。考虑了在氧化应激下与抑制剂转化密切相关的非抑制和抑制脂质氧化的动力学。特别关注了导致自由基引发的化学反应，这是氧化应激的关键阶段。讨论了羟基化酚和联苯酚侧链及酚环中取代基的影响以及浓度的影响。
