Development of a decision tree for mitochondrial dysfunction: uncoupling of oxidative phosphorylation

Date

2018

Authors

Enoch, S.J.
Schultz, T.W.
Popova, I.G.
Vasilev, K.G.
Mekenyan, O.G.

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Journal article

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Chemical Research in Toxicology, 2018; 31(8):814-820

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Abstract

Mitochondrial dysfunction is the result of a number of processes including the uncoupling of oxidative phosphorylation. This study outlines the development of a decision tree-based profiling scheme capable of assigning chemicals to one of six confidence-based categories. The decision tree is based on a set of structural alerts and physicochemical boundaries identified from a detailed study of the literature. The physicochemical boundaries define a chemical relationship with both log P and pKa. The study also outlines how the decision tree can be used to profile databases through an analysis of the publically available databases in the OECD QSAR Toolbox. This analysis enabled a set of additional structural alerts to be identified that are of concern for protonophoric ability. The decision tree will be incorporated in the OECD QSAR Toolbox V4.3. The intended usage is to group the chemicals into categories of chronic human health and environmental toxicological end points

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Link to a related website: http://researchonline.ljmu.ac.uk/id/eprint/8974/3/Development%20of%20a%20decision%20tree%20for%20mitochondrial%20dysfunction%20Uncoupling%20of%20oxidative%20phosphorylation.docx.pdf, Open Access via Unpaywall

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Copyright 2018 American Chemical Society

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