Beijing Key Laboratory of Active Substance Discovery and Drug ability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
J Asian Nat Prod Res. 2024 Nov;26(11):1328-1338. doi: 10.1080/10286020.2024.2362383. Epub 2024 Jun 30.
Histone deacetylase 6 (HDAC6) was a potential target for Alzheimer's disease (AD). In this study, a series of novel oxyevodiamine-based HDAC6 inhibitors with a variety of linker moieties were designed, synthesized and evaluated. Compound with a benzyl linker was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC value of 6.2 nM and was more than 200 fold selectivity over HDAC1. It also had lower cytotoxicity and higher anti-HO activity comparing with other derivatives. Compound might be a good lead as novel HDAC6 inhibitor for the treatment of AD.
组蛋白去乙酰化酶 6（HDAC6）是阿尔茨海默病（AD）的一个潜在靶点。在这项研究中，设计、合成并评价了一系列具有不同连接子的新型基于氧埃沃定的 HDAC6 抑制剂。带有苄基连接子的化合物 被鉴定为一种高效且选择性的 HDAC6 抑制剂。它对 HDAC6 的抑制作用的 IC 值为 6.2 nM，对 HDAC1 的选择性超过 200 倍。与其他衍生物相比，它还具有更低的细胞毒性和更高的抗 HO 活性。化合物 可能是一种治疗 AD 的新型 HDAC6 抑制剂的良好先导化合物。
