针对阿尔茨海默病中 Cu 的金属前药。
A Metallo Pro-Drug to Target Cu in the Context of Alzheimer's Disease.
机构信息
CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099 31077, Toulouse Cedex 4, France.
Université de Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France.
出版信息
Chemistry. 2018 Apr 6;24(20):5095-5099. doi: 10.1002/chem.201706049. Epub 2018 Feb 16.
Abstract
Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a Mn -based superoxide dismutase (SOD) mimic ([Mn (L)] , 1 ) as a pro-drug candidate to target Cu -associated events, namely, Cu -induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1 is able to remove Cu from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1 instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity.
摘要
阿尔茨海默病与氧化应激有关。在本通讯中，我们报告了使用锰基超氧化物歧化酶（SOD）模拟物（[Mn（L）]，1）作为针对铜相关事件的前药候选物，即铜诱导的活性氧（ROS）形成和淀粉样β（Aβ）肽聚集的调制。复合物 1能够从 Aβ中去除 Cu，阻止 ROS 的产生并防止 Aβ聚集的改变，就像相应的游离配体 LH 一样。在进一步的生物学应用中使用 1 代替 LH 将具有双重优势，既可以避免 LH 的细胞毒性，又可以受益于其已证明的 SOD 样活性。
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