Formation of a Toxic Quinoneimine Metabolite from Diclofenac: A Quantum Chemical Study

Author(s): Muthusamy Ramesh*, Prasad V. Bharatam

Journal Name: Drug Metabolism Letters

Volume 13 , Issue 1 , 2019

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Graphical Abstract:


Background: Diclofenac is a non-steroidal antiinflammatory drug. It is predominantly metabolized by CYP2C9. 4'-hydroxydiclofenac and its quinoneimine are the metabolites of diclofenac. However, few numbers of serious cases of idiosyncratic hepatotoxicity due to diclofenac metabolism were reported. The formation of the quinoneimine metabolite was found to be responsible for this idiosyncratic toxicity. Quinoneimine is an over-oxidized metabolite of diclofenac.

Method: In this work, computational studies were conducted to detail the formation of a quinoneimine metabolite from diclofenac. Further, the idiosyncratic toxicity of quinoneimine due to its reactivity was also investigated by quantum chemical analysis.

Results & Conclusion: The results demonstrate the possibility of formation of quinoneimine metabolite due to various factors that are involved in the metabolism of diclofenac. The present study may provide the structural in-sights during the drug development processes to avoid the metabolism directed idiosyncratic toxicity.

Keywords: Quantum chemical analysis, quinoneimine, diclofenac, idiosyncratic toxicity, CYP2C9, non-steroidal antiinflammatory drug.

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Year: 2019
Published on: 29 April, 2019
Page: [64 - 76]
Pages: 13
DOI: 10.2174/1872312812666180913120736

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