title: Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection.
abstract: Selected pyridinol analogues of the experimental neuroprotective drug idebenone have been synthesized and evaluated as antioxidants capable of preserving mitochondrial function. The compounds, having a different redox core but the same side chain as idebenone, exhibited a range of potencies, reflecting differences in their structures. The results obtained provide guidance in the design of such analogues with improved properties. Analogues were identified that have significantly improved antioxidant activity compared with idebenone in cultured lymphocytes, and which exhibit lesser inhibition of the electron transport chain.
authors.affiliation: Center for BioEnergetics, Biodesign Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, United States.
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Arce
authors.forename: Ruth
authors.initials: R
authors.lastname: Goldschmidt
authors.forename: Omar M
authors.initials: OM
authors.lastname: Khdour
authors.forename: Manikandadas M
authors.initials: MM
authors.lastname: Madathil
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jaruvangsanti
authors.forename: Sriloy
authors.initials: S
authors.lastname: Dey
authors.forename: David M
authors.initials: DM
authors.lastname: Fash
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Armstrong
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D009097:Multienzyme Complexes; D011728:Pyridones; D017382:Reactive Oxygen Species; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases