TY - JOUR
T1 - Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection
AU - Arce, Pablo M.
AU - Goldschmidt, Ruth
AU - Khdour, Omar
AU - Madathil, Manikandadas M.
AU - Jaruvangsanti, Jennifer
AU - Dey, Sriloy
AU - Fash, David M.
AU - Armstrong, Jeffrey S.
AU - Hecht, Sidney
N1 - Funding Information:
We thank Dr. Marco Flores (Arizona State University, Chemistry Department ESR facility) for assistance with the ESR experiment. This work was supported by a research grant from the Friedreich’s Ataxia Research Alliance.
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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, reflecting differences in their structures. The results obtained provide guidance in the design of such analogues with improved properties. Analogues were identified that have significantly improved antioxidant activity compared with idebenone in cultured lymphocytes, and which exhibit lesser inhibition of the electron transport chain.
AB - 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, reflecting differences in their structures. The results obtained provide guidance in the design of such analogues with improved properties. Analogues were identified that have significantly improved antioxidant activity compared with idebenone in cultured lymphocytes, and which exhibit lesser inhibition of the electron transport chain.
KW - Electron transport chain
KW - Idebenone
KW - Mitochondrial dysfunction
KW - Reactive oxygen species
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U2 - 10.1016/j.bmc.2012.07.005
DO - 10.1016/j.bmc.2012.07.005
M3 - Article
C2 - 22883028
AN - SCOPUS:84864971730
SN - 0968-0896
VL - 20
SP - 5188
EP - 5201
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 17
ER -