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ID: ALA4196108

Journal: J Med Chem

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

Authors: Lee HY, Fan SJ, Huang FI, Chao HY, Hsu KC, Lin TE, Yeh TK, Lai MJ, Li YH, Huang HL, Yang CR, Liou JP.

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.

CiteXplore: 30028616

DOI: 10.1021/acs.jmedchem.8b00151