Functional differences in epigenetic modulators - Superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies

Alan P. Kozikowski, Yufeng Chen, Arsen Gaysin, Bin Chen, Melissa A. D'Annibale, Carla M. Suto, Brett C. Langley

Research output: Contribution to journalArticle

Abstract

We compare the ability of two structurally different classes of epigenetic modulators, namely, histone deacetylase (HDAC) inhibitors containing either a hydroxamate or a mercaptoacetamide as the zinc binding group, to protect cortical neurons in culture from oxidative stress-induced death. This study reveals that some of the mercaptoacetamide-based HDAC inhibitors are fully protective, whereas the hydroxamates show toxicity at higher concentrations. Our present results appear to be consistent with the possibility that the mercaptoacetamide-based HDAC inhibitors interact with a different subset of the HDAC isozymes [less activity at HDAC1 and 2 correlates with less inhibitor toxicity], or alternatively, are interacting selectively with only the cytoplasmic HDACs that are crucial for protection from oxidative stress.

Original languageEnglish (US)
Pages (from-to)3054-3061
Number of pages8
JournalJournal of medicinal chemistry
Volume50
Issue number13
DOIs
StatePublished - Jun 28 2007

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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