title: Functional differences in epigenetic modulators-superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies.
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.
authors.affiliation: Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA. kozikowa@uic.edu
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kozikowski
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Chen
authors.forename: Arsen
authors.initials: A
authors.lastname: Gaysin
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Melissa A
authors.initials: MA
authors.lastname: D'Annibale
authors.forename: Carla M
authors.initials: CM
authors.lastname: Suto
authors.forename: Brett C
authors.initials: BC
authors.lastname: Langley
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000107:Acetylation; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000081:Acetamides; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D007527:Isoenzymes; D018696:Neuroprotective Agents; D013438:Sulfhydryl Compounds; D006655:Histone Deacetylases