摘要
This paper reports the development of a series of 5-aroylindolyl-substitued hydroxamic acids. N-hydroxy-4-((5-(4-methoxybenzoyl)-1H-indol-1-yl)methyl)benzamide (6) has potent inhibitory selectivity against histone deacetylase 6 (HDAC6) with an IC50 value of 3.92 nM. It decreases not only the level of phosphorylation of tau proteins but also the aggregation of tau proteins. Compound 6 also shows neuroprotective activity by triggering ubiquitination. In animal models, compound 6 is able to ameliorate the impaired learning and memory, and it crosses the blood-brain-barrier after oral administration. Compound 6 can be developed as a potential treatment for Alzheimer's disease in the future.
原文 | 英語 |
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頁(從 - 到) | 7087-7102 |
頁數 | 16 |
期刊 | Journal of Medicinal Chemistry |
卷 | 61 |
發行號 | 16 |
DOIs | |
出版狀態 | 已發佈 - 8月 23 2018 |
ASJC Scopus subject areas
- 分子醫學
- 藥物發現