5‑Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer’s Disease Phenotypes

This paper reports
the development of a series of 5-aroylindolyl-substituted
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.