Losada-Barreiro Sonia, Bravo-Díaz Carlos
Universidad de Vigo, Fac. Química, Dpto Química Física, 36200, Vigo, Spain; Requimte, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007, Portugal.
Universidad de Vigo, Fac. Química, Dpto Química Física, 36200, Vigo, Spain.
Eur J Med Chem. 2017 Jun 16;133:379-402. doi: 10.1016/j.ejmech.2017.03.061. Epub 2017 Mar 29.
The oxidation of bioorganic materials by air and, particularly, the oxidative stress involved in the cell loss and other pathologies associated with neurodegenerative diseases (NDs) are of enormous social and economic importance. NDs generally involve free radical reactions, beginning with the formation of an initiating radical by some redox, thermal or photochemical process, causing nucleic acid, protein and lipid oxidations and the production of harmful oxidative products. Physically, persons afflicted by NDs suffer progressive loss of memory and thinking ability, mood swings, personality changes, and loss of independence. Therefore, the development of antioxidant strategies to retard or minimize the oxidative degradation of bioorganic materials has been, and still is, of paramount importance. While we are aware of the importance of investigating the biological and medical aspects of the diseases, elucidation of the associated chemistry is crucial to understanding their progression, heading to intelligent chemical intervention to find more efficient therapies to prevent or delay the onset of the diseases. Accordingly, this review aims to provide the reader with a chemical base to understand the behavior and properties of the reactive oxygen species involved and of typical radical scavengers such as polyphenolic antioxidants. Some discussion on the structures of the various species, their formation, chemical reactivities and lifetimes is included. The ultimate goal is to understand how, when and where they form, how far they travel prior to react, which molecules are their targets, and how we can, eventually, control their activity to minimize their impact by means of chemical methods. Recent strategies explore chemical modifications of the hydrophobicity of potent, natural antioxidants to improve their efficiency by fine-tuning their concentrations at the reaction site.
生物有机材料被空气氧化，尤其是与神经退行性疾病（NDs）相关的细胞损失及其他病变过程中涉及的氧化应激，具有巨大的社会和经济意义。NDs通常涉及自由基反应，始于通过某些氧化还原、热或光化学过程形成引发自由基，进而导致核酸、蛋白质和脂质氧化，并产生有害的氧化产物。从身体方面来看，患有NDs的人会逐渐丧失记忆和思维能力、出现情绪波动、性格改变以及失去独立生活能力。因此，开发抗氧化策略以延缓或最小化生物有机材料的氧化降解一直以来都至关重要，并且现在仍然如此。虽然我们意识到研究这些疾病的生物学和医学方面的重要性，但阐明相关化学过程对于理解其发展进程至关重要，这有助于进行智能化学干预，以找到更有效的疗法来预防或延缓疾病的发作。因此，本综述旨在为读者提供一个化学基础，以了解所涉及的活性氧物种以及典型自由基清除剂（如多酚类抗氧化剂）的行为和性质。文中还包括对各种物种的结构、它们的形成、化学反应性和寿命的一些讨论。最终目标是了解它们如何、何时以及在何处形成，在反应之前它们能传播多远，哪些分子是它们的作用靶点，以及我们最终如何通过化学方法控制它们的活性以最小化其影响。最近的策略探索了对强效天然抗氧化剂的疏水性进行化学修饰，通过微调它们在反应位点的浓度来提高其效率。
