Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection

• Published in: Bioorganic & medicinal chemistry Vol. 20; no. 17; pp. 5188 - 5201
• Main Authors: Arce, Pablo M., Goldschmidt, Ruth, Khdour, Omar M., Madathil, Manikandadas M., Jaruvangsanti, Jennifer, Dey, Sriloy, Fash, David M., Armstrong, Jeffrey S., Hecht, Sidney M.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2012; Elsevier
• Subjects: Animals; antagonists & inhibitors; antioxidant activity; Antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Biochemistry & Molecular Biology; Biological and medical sciences; Cattle; Cell Survival; Cell Survival - drug effects; chemical synthesis; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytoprotection; Cytoprotection - drug effects; Dose-Response Relationship, Drug; drug effects; Drugs; Electron transport chain; enzymology; Humans; Idebenone; Life Sciences & Biomedicine; Lipid Peroxidation; Lipid Peroxidation - drug effects; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - metabolism; Medical sciences; metabolism; Mitochondria; Mitochondria, Heart; Mitochondria, Heart - drug effects; Mitochondria, Heart - enzymology; Mitochondria, Heart - metabolism; Mitochondrial dysfunction; Mitochondrial Membranes; Mitochondrial Membranes - drug effects; Mitochondrial Membranes - metabolism; Molecular Structure; Multienzyme Complexes; Multienzyme Complexes - antagonists & inhibitors; Multienzyme Complexes - metabolism; NADH, NADPH Oxidoreductases; NADH, NADPH Oxidoreductases - antagonists & inhibitors; NADH, NADPH Oxidoreductases - metabolism; Neuroprotection; pharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Pyridones; Pyridones - chemical synthesis; Pyridones - chemistry; Pyridones - pharmacology; Reactive Oxygen Species; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; Science & Technology; Structure-Activity Relationship; Tumor Cells, Cultured; Electron transport chain; Idebenone; Reactive oxygen species; Mitochondrial dysfunction; OXIDATIVE STRESS; FRIEDREICHS-ATAXIA; REACTIVITY; NEURODEGENERATIVE DISEASES; PERMEABILITY TRANSITION; COMPLEX-I; GLUTATHIONE; DYSFUNCTION; RESPIRATORY COMPLEXES; Oxidative stress; Psychotropic; Quinone; Benzoquinone derivatives; Antioxidant; Respiratory chain; Mitochondria; Cytoprotector; Nootropic agent; Cell respiration

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, reflect...