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 IC 50 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.

Original languageEnglish
Pages (from-to)7087-7102
Number of pages16
JournalJournal of Medicinal Chemistry
Issue number16
Publication statusPublished - Aug 23 2018

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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