Journal
CHEMMEDCHEM
Volume 4, Issue 5, Pages 842-852Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.200800461
Keywords
benzamides; HDAC inhibitors; neurological agents; oxidative stress; prodrugs
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Funding
- Alzheimer's Drug Discovery Foundation
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We compare three structurally different classes of histone deacetylase (HDAC) inhibitors that contain benzamide, hydroxamate, or thiol groups as the zinc binding group (ZBG) for their ability to protect cortical neurons in culture from cell death induced by oxidative stress. This study reveals that none of the benzamide-based HDAC inhibitors (HDACIs) provides any neuroprotection whatsoever, in distinct contrast to HDACIs that contain other ZBGs. Some of the sulfur-containing HDACIs, namely the thiols, thioesters, and disulfides present modest neuroprotective activity but show toxicity at higher concentrations. Taken together, these data demonstrate that the HDAC6-selective mercaptoacetamides that were reported previously provide them best protection in the homocysteic acid model of oxidative stress, thus further supporting their study in animal models of neurodegenerative diseases.
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