Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection

Pablo M. Arce; Ruth Goldschmidt; Omar Khdour; Manikandadas M. Madathil; Jennifer Jaruvangsanti; Sriloy Dey; David M. Fash; Jeffrey S. Armstrong; Sidney Hecht

doi:10.1016/j.bmc.2012.07.005

Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection

Pablo M. Arce, Ruth Goldschmidt, Omar Khdour, Manikandadas M. Madathil, Jennifer Jaruvangsanti, Sriloy Dey, David M. Fash, Jeffrey S. Armstrong, Sidney Hecht

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	5188-5201
Number of pages	14
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2012.07.005
State	Published - Sep 1 2012

Keywords

Electron transport chain
Idebenone
Mitochondrial dysfunction
Reactive oxygen species

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2012.07.005

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title = "Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection",

abstract = "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.",

keywords = "Electron transport chain, Idebenone, Mitochondrial dysfunction, Reactive oxygen species",

author = "Arce, {Pablo M.} and Ruth Goldschmidt and Omar Khdour and Madathil, {Manikandadas M.} and Jennifer Jaruvangsanti and Sriloy Dey and Fash, {David M.} and Armstrong, {Jeffrey S.} and Sidney Hecht",

note = "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{\textquoteright}s Ataxia Research Alliance. ",

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doi = "10.1016/j.bmc.2012.07.005",

language = "English (US)",

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journal = "Bioorganic and Medicinal Chemistry",

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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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JO - Bioorganic and Medicinal Chemistry

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Analysis of the structural and mechanistic factors in antioxidants that preserve mitochondrial function and confer cytoprotection

Abstract

Keywords

ASJC Scopus subject areas

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