基于氧代乙二胺的组蛋白去乙酰化酶 6 抑制剂的设计、合成和生物活性。

IF 1.3 3区医学 Q3 CHEMISTRY, APPLIED

Journal of Asian Natural Products Research Pub Date : 2024-06-26 DOI:10.1080/10286020.2024.2362383

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引用次数: 0

摘要

组蛋白去乙酰化酶6（HDAC6）是阿尔茨海默病（AD）的潜在靶点。本研究设计、合成并评估了一系列新型氧代乙二胺基 HDAC6 抑制剂，这些抑制剂具有多种连接基团。带有苄基连接基的化合物 12 被鉴定为一种高效力、高选择性的 HDAC6 抑制剂。它抑制 HDAC6 的 IC50 值为 6.2 nM，比 HDAC1 的选择性高出 200 多倍。与其他衍生物相比，它还具有更低的细胞毒性和更高的体外抗 H2O2 活性。化合物 12 可能是治疗注意力缺失症的新型 HDAC6 抑制剂。

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Design, synthesis and biological activity of oxyevodiamine-based histone deacetylase 6 inhibitors

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 12 with a benzyl linker was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC₅₀ value of 6.2 nM and was more than 200 fold selectivity over HDAC1. It also had lower cytotoxicity and higher anti-H₂O₂ activity in vitro comparing with other derivatives. Compound 12 might be a good lead as novel HDAC6 inhibitor for the treatment of AD.

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来源期刊

Journal of Asian Natural Products Research 医学-药学

CiteScore

3.20

自引率

5.90%

发文量

审稿时长

2.3 months

期刊介绍： The Journal of Asian Natural Products Research (JANPR) publishes chemical and pharmaceutical studies in the English language in the field of natural product research on Asian ethnic medicine. The journal publishes work from scientists in Asian countries, e.g. China, Japan, Korea and India, including contributions from other countries concerning natural products of Asia. The journal is chemistry-orientated. Major fields covered are: isolation and structural elucidation of natural constituents (including those for non-medical uses), synthesis and transformation (including biosynthesis and biotransformation) of natural products, pharmacognosy, and allied topics. Biological evaluation of crude extracts are acceptable only as supporting data for pure isolates with well-characterized structures. All published research articles in this journal have undergone rigorous peer review, based on initial editor screening and anonymized refereeing by at least two expert referees.