V. A. Institute of Chemical Kinetics and Combustion, Institutskaya Str., 3, Novosibirsk, 630090, Russia.
Novosibirsk State University, Pirogova Str., 2, 630090, Novosibirsk, Russia.
J Biol Inorg Chem. 2019 May;24(3):331-341. doi: 10.1007/s00775-019-01650-9. Epub 2019 Mar 13.
Copper ions can catalyze the production of free oxygen radicals (•OH and •OOH) similar to iron ions. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced toxicity in copper-related diseases where there is an increase in copper levels and also when Cu homeostasis and regulation are disrupted. An antioxidant/chelator inhibiting Cu-induced oxidative damage could play a significant role in the treatment of such Cu-related diseases. Deferiprone has high affinity for copper binding and can be considered for the potential treatment of copper toxicity and overloading conditions, such as Wilson's disease. In the present study, the ability of deferiprone to inhibit the production of hydroxyl radicals catalyzed by copper ions was elucidated using an Electron Paramagnetic Resonance (EPR) spin trapping technique. The values of g-factors and hyperfine splitting constants were calculated for Cu(II)-deferiprone 1:1 complex: (a = 58.5 G, g = 2.1667) and 1:2 complex: (a = 73.0 G, g = 2.1378). The TMIO spin trap (2,2,4-trimethyl-2H-imidazole-1-oxide) was used for the detection of free radicals formed in Fenton-like copper-catalyzed reactions. It was demonstrated that the interaction of deferiprone with Cu ions completely inhibited hydroxyl radical (•OH) production in the presence of hydrogen peroxide. It was found also that deferiprone inhibits Cu-induced oxidation of linoleic acid in micellar solution. In addition to existing data for water solutions, the affinity of deferiprone for copper binding in non-aqueous environment has been elucidated.
铜离子可以像铁离子一样催化游离氧自由基（•OH 和•OOH）的生成。铜诱导毒性的能力通常归因于铜相关疾病中铜水平的增加，以及当铜的动态平衡和调节被破坏时。一种能够抑制铜诱导氧化损伤的抗氧化剂/螯合剂，可能在治疗这种铜相关疾病方面发挥重要作用。去铁酮对铜结合具有高亲和力，可考虑用于治疗铜毒性和超负荷情况，如威尔逊氏病。在本研究中，使用电子顺磁共振（EPR）自旋捕获技术阐明了去铁酮抑制铜离子催化羟基自由基生成的能力。计算了 Cu(II)-去铁酮 1:1 配合物的 g 因子和超精细分裂常数：（a = 58.5 G，g = 2.1667）和 1:2 配合物：（a = 73.0 G，g = 2.1378）。TMIO 自旋捕获剂（2,2,4-三甲基-2H-咪唑-1-氧化物）用于检测 Fenton 样铜催化反应中形成的自由基。结果表明，去铁酮与铜离子的相互作用在存在过氧化氢的情况下完全抑制了羟基自由基（•OH）的生成。还发现去铁酮抑制了铜诱导的胶束溶液中亚油酸的氧化。除了现有的水溶液数据外，还阐明了去铁酮在非水环境中与铜结合的亲和力。
