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) |
|---|---|
| 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 |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Functional differences in epigenetic modulators - Superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies. / Kozikowski, Alan P.; Chen, Yufeng; Gaysin, Arsen; Chen, Bin; D'Annibale, Melissa A.; Suto, Carla M.; Langley, Brett C.
In: Journal of Medicinal Chemistry, Vol. 50, No. 13, 28.06.2007, p. 3054-3061.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Functional differences in epigenetic modulators - Superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies
AU - Kozikowski, Alan P.
AU - Chen, Yufeng
AU - Gaysin, Arsen
AU - Chen, Bin
AU - D'Annibale, Melissa A.
AU - Suto, Carla M.
AU - Langley, Brett C.
PY - 2007/6/28
Y1 - 2007/6/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34347224016&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34347224016&partnerID=8YFLogxK
U2 - 10.1021/jm070178x
DO - 10.1021/jm070178x
M3 - Article
C2 - 17539623
AN - SCOPUS:34347224016
VL - 50
SP - 3054
EP - 3061
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 13
ER -