5-Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer's Disease Phenotypes.
J Med Chem
; 61(16): 7087-7102, 2018 08 23.
Article
em En
| MEDLINE
| ID: mdl-30028616
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fármacos Neuroprotetores
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Inibidores de Histona Desacetilases
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Desacetilase 6 de Histona
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Indóis
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article