Synthesis and bioactivity evaluation of glycosylated resveratrol derivatives as antioxidative neuroprotection agents against cerebral Ischemia-Reperfusion injury

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2024-09-02 DOI:10.1016/j.bioorg.2024.107791

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Abstract

Resveratrol (Res) has long been discovered to have antioxidant effects to prevent such as oxidation, inflammation, neurodegeneration and age-related diseases. However, its poor water solubility, low bioavailability and instability have become a barrier to its pharmaceutical application. In order to improve the neuroprotective effects and develop more potential usage of Res, three Res derivatives containing one or two glucose groups, i.e., Res-Glu1, Res-Glu2 and Res-Glu3, were designed and synthesized through click reaction. Res-Glu1, Res-Glu2 and Res-Glu3 were tested being better water solubility and stability compared to Res. Res derivatives reduced •OH radicals-induced DNA damage. PC12 assays indicated that glucosylated Res derivatives could alleviate H₂O₂-induced neurotoxicity and reduce intracellular ROS generation, demonstrating their neuroprotective effects. In addition, Res derivatives enhanced the protective effects on cerebral ischemia–reperfusion injury in rats. Res-Glu3 displayed the best neuroprotective effects among the three derivatives.

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糖基化白藜芦醇衍生物作为抗脑缺血再灌注损伤的抗氧化神经保护剂的合成与生物活性评估

白藜芦醇（Res）很早就被发现具有抗氧化作用，可预防氧化、炎症、神经退化和与年龄有关的疾病。然而，白藜芦醇的水溶性差、生物利用率低和不稳定性成为其制药应用的障碍。为了提高 Res 的神经保护作用并开发其更多潜在用途，研究人员通过点击反应设计并合成了三种含有一个或两个葡萄糖基团的 Res 衍生物，即 Res-Glu1、Res-Glu2 和 Res-Glu3。经测试，与 Res 相比，Res-Glu1、Res-Glu2 和 Res-Glu3 具有更好的水溶性和稳定性。Res 衍生物可减少-OH 自由基诱导的 DNA 损伤。PC12 试验表明，葡萄糖基化的 Res 衍生物可减轻 H2O2 诱导的神经毒性并减少细胞内 ROS 的生成，这证明了它们的神经保护作用。此外，Res 衍生物还能增强对大鼠脑缺血再灌注损伤的保护作用。在三种衍生物中，Res-Glu3 的神经保护效果最好。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.