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: Ruth Goldschmidt, Pablo M Arce, Omar M Khdour, Valérie C Collin, Sriloy Dey, Jennifer Jaruvangsanti, David M Fash, Sidney M Hecht
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 21 Issue 4 Pg. 969-78 (Feb 15 2013) ISSN: 1464-3391 [Electronic] England
• PMID: 23313093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• 2-(N,N-dimethylamino)-4-hexadecyl-6-methylpyrimidin-5-ol
• 4-decyl-2-(N,N-dimethylamino)-6-methylpyrimidin-5-ol
• Antioxidants
• Multienzyme Complexes
• Neuroprotective Agents
• Pyrimidines
• Reactive Oxygen Species
• Ubiquinone
• Adenosine Triphosphate
• NADH oxidase
• NADH, NADPH Oxidoreductases
• coenzyme Q10
• Glutathione
• idebenone

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Antioxidants (chemical synthesis, chemistry, toxicity)
• Cattle
• Cell Line
• Cell Survival (drug effects)
• Drug Design
• Glutathione (metabolism)
• Humans
• Lymphocytes (drug effects, metabolism)
• Mitochondria (enzymology, metabolism)
• Multienzyme Complexes (antagonists & inhibitors, metabolism)
• NADH, NADPH Oxidoreductases (antagonists & inhibitors, metabolism)
• Neurodegenerative Diseases (metabolism, pathology)
• Neuroprotective Agents (chemical synthesis, chemistry, toxicity)
• Pyrimidines (chemical synthesis, chemistry, toxicity)
• Reactive Oxygen Species (metabolism)
• Ubiquinone (analogs & derivatives, chemical synthesis, chemistry, genetics, metabolism, toxicity)