5-Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer's Disease Phenotypes

Hsueh Yun Lee, Sheng Jun Fan, Fang I. Huang, Hsin Yi Chao, Kai Cheng Hsu, Tony Eight Lin, Teng Kuang Yeh, Mei Jung Lai, Yu Hsuan Li, Hsiang Ling Huang, Chia Ron Yang, Jing Ping Liou

Research output: Contribution to journalArticle

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.

LanguageEnglish
JournalJournal of Medicinal Chemistry
DOIs
Publication statusAccepted/In press - Jan 29 2018

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tau Proteins
Histone Deacetylase Inhibitors
Alzheimer Disease
Hydroxamic Acids
Phenotype
Histone Deacetylases
Ubiquitination
Blood-Brain Barrier
Inhibitory Concentration 50
Oral Administration
Animal Models
Phosphorylation
Learning
Therapeutics
benzamide

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 journalArticle

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. / 5-Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer's Disease Phenotypes. In: Journal of Medicinal Chemistry. 2018.
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AU - Hsu, Kai Cheng

AU - Lin, Tony Eight

AU - Yeh, Teng Kuang

AU - Lai, Mei Jung

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