title: Effects of cytoprotective antioxidants on lymphocytes from representative mitochondrial neurodegenerative diseases.
abstract: Two new aza analogues of the neuroprotective agent idebenone have been synthesized and characterized. Their antioxidant activity, and ability to augment ATP levels have been evaluated in several different cell lines having suboptimal mitochondrial function. Both compounds were found to be good ROS scavengers, and to protect the cells from oxidative stress induced by glutathione depletion. The compounds were more effective than idebenone in neurodegenerative disease cells. These novel pyrimidinol derivatives were also shown to augment ATP levels in coenzyme Q(10)-deficient human lymphocytes. The more lipophilic side chains attached to the pyrimidinol redox core in these compounds resulted in less inhibition of the electron transport chain and improved antioxidant activity.
authors: Center for BioEnergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors: Ruth
authors: R
authors: Goldschmidt
authors: Pablo M
authors: PM
authors: Arce
authors: Omar M
authors: OM
authors: Khdour
authors: Valérie C
authors: VC
authors: Collin
authors: Sriloy
authors: S
authors: Dey
authors: Jennifer
authors: J
authors: Jaruvangsanti
authors: David M
authors: DM
authors: Fash
authors: Sidney M
authors: SM
authors: Hecht
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000633:toxicity
chemical_list: C582855:2-(N,N-dimethylamino)-4-hexadecyl-6-methylpyrimidin-5-ol; C582854:4-decyl-2-(N,N-dimethylamino)-6-methylpyrimidin-5-ol; D000975:Antioxidants; D009097:Multienzyme Complexes; D018696:Neuroprotective Agents; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D000255:Adenosine Triphosphate; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; C024989:coenzyme Q10; D005978:Glutathione; C036619:idebenone