Effects of alkyl side chain modification of coenzyme Q(10) on mitochondrial respiratory chain function and cytoprotection

• Published in: Bioorganic & medicinal chemistry Vol. 21; no. 8; pp. 2346 - 2354
• Main Authors: Fash, David M., Khdour, Omar M., Sahdeo, Sunil J., Goldschmidt, Ruth, Jaruvangsanti, Jennifer, Dey, Sriloy, Arce, Pablo M., Collin, Valerie C., Cortopassi, Gino A., Hecht, Sidney M.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier 15.04.2013
• Subjects: Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; CELLS; Reactive oxygen species; OXIDATIVE STRESS; ANALOGS; Coenzyme Q; Oxygen consumption; UBIQUINONE; Electron transport chain; REACTIVE OXYGEN; ANTIOXIDANT; DYSFUNCTION; CORRELATE; Cytoprotection
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.01.075

The effect of the alkyl side chain length of coenzyme Q(10) on mitochondrial respiratory chain function has been investigated by the use of synthetic ubiquinone derivatives. Three analogues (3, 4 and 6) were identified that exhibited significantly improved effects on mitochondrial oxygen consumption and mitochondrial membrane potential, and also conferred significant cytoprotection on cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate. The analogues also exhibited lesser inhibition of the electron transport chain than idebenone. The results obtained provide guidance for the design of CoQ(10) analogues with improved activity compared to that of idebenone (1), the latter of which is undergoing evaluation in the clinic as a therapeutic agent. (C) 2013 Elsevier Ltd. All rights reserved.