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 language | English (US) |
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Pages (from-to) | 3054-3061 |
Number of pages | 8 |
Journal | Journal of medicinal chemistry |
Volume | 50 |
Issue number | 13 |
DOIs | |
State | Published - Jun 28 2007 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery