title: Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection.
abstract: The effect of the alkyl side chain length of coenzyme Q10 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 CoQ10 analogues with improved activity compared to that of idebenone (1), the latter of which is undergoing evaluation in the clinic as a therapeutic agent.
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Fash
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Omar M
authors.initials: OM
authors.lastname: Khdour
authors.affiliation: Department of Molecular Biosciences, University of California, Davis, CA 95616, USA.
authors.forename: Sunil J
authors.initials: SJ
authors.lastname: Sahdeo
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Goldschmidt
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jaruvangsanti
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Sriloy
authors.initials: S
authors.lastname: Dey
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Arce
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Valérie C
authors.initials: VC
authors.lastname: Collin
authors.affiliation: Department of Molecular Biosciences, University of California, Davis, CA 95616, USA. Electronic address: gcortopassi@ucdavis.edu.
authors.forename: Gino A
authors.initials: GA
authors.lastname: Cortopassi
authors.affiliation: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA. Electronic address: sidney.hecht@asu.edu.
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D019610:Cytoprotection; D004579:Electron Transport / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014451:Ubiquinone; C024989:coenzyme Q10