HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Studies of benzamide- and thiol-based histone deacetylase inhibitors in models of oxidative-stress-induced neuronal death: identification of some HDAC3-selective inhibitors.

Abstract
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 the best protection in the homocysteic acid model of oxidative stress, thus further supporting their study in animal models of neurodegenerative diseases.
AuthorsYufeng Chen, Rong He, Yihua Chen, Melissa A D'Annibale, Brett Langley, Alan P Kozikowski
JournalChemMedChem (ChemMedChem) Vol. 4 Issue 5 Pg. 842-52 (May 2009) ISSN: 1860-7187 [Electronic] Germany
PMID19350613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzamides
  • Carrier Proteins
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Neuroprotective Agents
  • Protein Isoforms
  • Sulfhydryl Compounds
  • zinc-binding protein
  • Histone Deacetylases
Topics
  • Animals
  • Apoptosis
  • Benzamides (chemical synthesis, chemistry, pharmacology)
  • Carrier Proteins (metabolism)
  • Cells, Cultured
  • Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases (metabolism)
  • Hydroxamic Acids (chemical synthesis, chemistry, pharmacology)
  • Models, Biological
  • Neurons (drug effects)
  • Neuroprotective Agents (chemical synthesis, chemistry, pharmacology)
  • Oxidative Stress
  • Protein Isoforms (antagonists & inhibitors, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Sulfhydryl Compounds (chemistry)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: