Paper
5-Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer's Disease Phenotypes.
Published Jul 20, 2018 · Hsueh-Yun Lee, Sheng-jun Fan, Fang-I Huang
Journal of medicinal chemistry
Q1 SJR score
53
Citations
2
Influential Citations
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.
Study Snapshot
Compound 6 shows potential as a selective HDAC6 inhibitor, reducing tau protein phosphorylation and aggregation, and showing neuroprotective activity, making it a potential Alzheimer's disease treatment.
PopulationOlder adults (50-71 years)
Sample size24
MethodsObservational
OutcomesBody Mass Index projections
ResultsSocial networks mitigate obesity in older groups.
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