Department of Pharmacy, University of Naples Federico II, 80131, Naples, Italy.
Department of Chemical Sciences, University of Naples Federico II, 80126, Naples, Italy.
Dalton Trans. 2023 Jun 27;52(25):8549-8557. doi: 10.1039/d3dt01110k.
Neurodegenerative diseases are often characterized by the formation of aggregates of amyloidogenic peptides and proteins, facilitating the formation of neurofibrillary plaques. In this study, we investigate a series of Ru-complexes sharing three-legged piano-stool structures based on the arene ring and glucosylated carbene ligands. The ability of these complexes to bind amyloid His-peptides was evaluated by ESI-MS, and their effects on the aggregation process were investigated through ThT and Tyr fluorescence emission. The complexes were demonstrated to bind the amyloidogenic peptides even with different mechanisms and kinetics depending on the chemical nature of the ligands around the Ru(II) ion. TEM analysis detected the disaggregation of typical fibers caused by the presence of Ru-compounds. Overall, our results show that the Ru-complexes can modulate the aggregation of His-amyloids and can be conceived as good lead compounds in the field of novel anti-aggregating agents in neurodegeneration.
神经退行性疾病的特征通常是淀粉样肽和蛋白质的聚集物的形成，这促进了神经原纤维缠结的形成。在这项研究中，我们研究了一系列基于芳环和糖基化卡宾配体的具有三足钢琴凳结构的 Ru 配合物。通过 ESI-MS 评估了这些配合物与淀粉样 His-肽结合的能力，并通过 ThT 和 Tyr 荧光发射研究了它们对聚集过程的影响。这些配合物被证明可以结合淀粉样肽，即使它们的结合机制和动力学因 Ru(II)离子周围配体的化学性质而异。TEM 分析检测到典型纤维的解聚是由 Ru 化合物的存在引起的。总的来说，我们的结果表明，Ru 配合物可以调节 His-淀粉样蛋白的聚集，并且可以被视为神经退行性疾病中新型抗聚集剂领域的良好先导化合物。
