Department of Chemistry and Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
Department of Chemistry and Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
Bioorg Med Chem Lett. 2024 Jul 15;107:129788. doi: 10.1016/j.bmcl.2024.129788. Epub 2024 May 11.
Effectively inhibition of amyloid β (Aβ) aggregation is considered an important method for treatment of the Alzheimer's disease. Herein, inspired by the ability of trans-clovamide to effectively inhibit Aβ aggregation, we synthesized a series of structurally related catecholamine derivatives and tested them as Aβ aggregation inhibitors using the Thioflavin T assay. The results show that they demonstrated a higher inhibitory rate against Aβ aggregation. Furthermore, these compounds exhibited high water solubilities and low cytotoxicities. Additionally, transmission electron microscopy images and dynamic light scattering of their Aβ aggregations were observed. Docking simulations revealed that the catechol moiety of the synthesized compounds can form hydrogen bonds with the key regions of Aβ and thereby inhibit Aβ aggregation.
有效抑制淀粉样蛋白β（Aβ）聚集被认为是治疗阿尔茨海默病的重要方法。受邻苯二酰亚胺抑制 Aβ聚集能力的启发，我们合成了一系列结构相关的儿茶酚胺衍生物，并通过噻唑蓝 T 试验测试它们作为 Aβ 聚集抑制剂的能力。结果表明，它们对 Aβ 聚集具有更高的抑制率。此外，这些化合物具有高水溶性和低细胞毒性。此外，还观察了它们对 Aβ 聚集的透射电子显微镜图像和动态光散射。对接模拟表明，合成化合物的儿茶酚部分可以与 Aβ 的关键区域形成氢键，从而抑制 Aβ 聚集。
