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

15 Citations (Scopus)

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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