Abstract
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.
| Original language | English |
|---|---|
| Journal | Journal of Medicinal Chemistry |
| DOIs | |
| Publication status | Accepted/In press - Jan 29 2018 |
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ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Cite this
5-Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer's Disease Phenotypes. / Lee, Hsueh Yun; Fan, Sheng Jun; Huang, Fang I.; Chao, Hsin Yi; Hsu, Kai Cheng; Lin, Tony Eight; Yeh, Teng Kuang; Lai, Mei Jung; Li, Yu Hsuan; Huang, Hsiang Ling; Yang, Chia Ron; Liou, Jing Ping.
In: Journal of Medicinal Chemistry, 29.01.2018.Research output: Contribution to journal › Article
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TY - JOUR
T1 - 5-Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer's Disease Phenotypes
AU - Lee, Hsueh Yun
AU - Fan, Sheng Jun
AU - Huang, Fang I.
AU - Chao, Hsin Yi
AU - Hsu, Kai Cheng
AU - Lin, Tony Eight
AU - Yeh, Teng Kuang
AU - Lai, Mei Jung
AU - Li, Yu Hsuan
AU - Huang, Hsiang Ling
AU - Yang, Chia Ron
AU - Liou, Jing Ping
PY - 2018/1/29
Y1 - 2018/1/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85050635071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050635071&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.8b00151
DO - 10.1021/acs.jmedchem.8b00151
M3 - Article
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
ER -