Multimechanism biological profiling of tetrahydro-β-carboline analogues as selective HDAC6 inhibitors for the treatment of Alzheimer's disease.

With the intensive research on the pathogenesis of Alzheimer's disease (AD), inhibition of HDAC6 appears to be a potential therapeutic approach for AD. In this paper, a series of tetrahydro-β-carboline derivatives with hydroxamic acid group were fast synthesized. Among all, the most potent 15 selectively inhibited HDAC6 with IC of 15.

Tetrahydro-β-carboline derivatives as potent histone deacetylase 6 inhibitors with broad-spectrum antiproliferative activity.

A series of tetrahydro-β-carboline (THβC)-based hydroxamic acids were rationally designed and synthesized as novel selective HDAC6 inhibitors (sHDAC6is) by the application of scaffold hopping strategy. Several THβC analogues were highly potent (IC < 5 nM) and selective against HDAC6 enzyme and exhibited good antiproliferative activity against human multiple myeloma (MM) cell. Molecular docking interpreted the structure activity relationship (SAR).

Discovery of indole-piperazine derivatives as selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting activities and neuroprotective activities.

Novel indole-piperazine derivatives with a hydroxamic acid moiety were designed and synthesized as selective histone deacetylase 6 (HDAC6) inhibitors. In enzymatic assays, all compounds exhibited nanomolar IC values. N-hydroxy-4-((4-(7-methyl-1H-indole-3-carbonyl)piperazin-1-yl)methyl)benzamide, 9c, was the most potent HDAC6 inhibitor (IC, 13.