Zonzin Martina, Chianese Martina, Squarcina Andrea, Dereje Degnet Melese, Campofelice Ambra, Da Fermo Alessia, Belluti Federica, Marino Nadia, Dębicki Filip, Kotynia Aleksandra, Marciniak Aleksandra, Brasuń Justyna, Carraro Mauro
Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padova, Italy.
Department of Chemistry, Ludwig-Maximilians Universität (LMU), Butenandtstr, 5-13, 81377 München, Germany.
Molecules. 2025 Aug 19;30(16):3419. doi: 10.3390/molecules30163419.
Oxidative stress, driven by excess reactive oxygen species (ROS), is a key factor in the progression of neurodegenerative diseases like Alzheimer's disease (AD). In this context, copper dysregulation can also contribute to this imbalance, being responsible for enhanced ROS production, so that copper scavenging has been investigated as a possible therapeutic strategy. This study investigates the behavior of two isostructural ligands, featuring an NO donor set, that effectively chelate Cu(II) in aqueous solution. Interestingly, their resulting mono- or dinuclear copper complexes feature a coordination environment suitable to foster antioxidant activity. By transforming copper's oxidant potential into antioxidant action, these systems may reduce copper-induced oxidative damage. The work examines the pH-dependent metal-binding behavior of the ligands, the catalytic properties of the resulting complexes under physiological conditions, and their ability to inhibit β-amyloid peptide aggregation.
由过量活性氧（ROS）驱动的氧化应激是阿尔茨海默病（AD）等神经退行性疾病进展的关键因素。在这种情况下，铜失调也会导致这种失衡，导致ROS生成增加，因此铜清除已作为一种可能的治疗策略进行研究。本研究调查了两种具有等结构且含有NO供体基团的配体在水溶液中有效螯合Cu(II)的行为。有趣的是，它们形成的单核或双核铜配合物具有适合促进抗氧化活性的配位环境。通过将铜的氧化电位转化为抗氧化作用，这些体系可能减少铜诱导的氧化损伤。这项工作研究了配体的pH依赖性金属结合行为、所得配合物在生理条件下的催化性质以及它们抑制β-淀粉样肽聚集的能力。
