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

Journal of Medicinal Chemistry
Hsueh-Yun LeeJing-Ping Liou

Abstract

This paper reports the development of a series of 5-aroylindolyl-substituted hydroxamic acids. N-Hydroxy-4-((5-(4-methoxybenzoyl)-1 H-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.

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Citations

Dec 24, 2019·Expert Opinion on Therapeutic Patents·Sida Shen, Alan P Kozikowski
Jan 1, 2020·Biomolecules·Gabriela Dumitrita StanciuDaniela Carmen Ababei
Feb 6, 2020·Expert Opinion on Therapeutic Patents·Chunlong ZhaoYingjie Zhang
May 17, 2019·Neural Plasticity·Chao-Chao YuLi-Hong Kong
Nov 10, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Samir MehndirattaHsueh-Yun Lee
Nov 11, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sravani PulyaBalaram Ghosh
Dec 31, 2020·Cells·Patrizia LoPresti
Mar 6, 2021·Bioorganic & Medicinal Chemistry·Maurício Temotheo TavaresRoberto Parise-Filho
Apr 13, 2021·The Journal of Organic Chemistry·Wangyujing HanShunying Liu
Apr 21, 2021·Neuroscience Letters·Graziella CappellettiChiara Rolando

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