Fragmentation of the quinoxaline N-oxide bond to the ˙OH radical upon one-electron bioreduction

Yadav, Pooja; Marshall, Andrew J.; Reynisson, Jóhannes; Denny, William A.; Hay, Michael P.; Anderson, Robert F.

Abstract

The ˙OH radical is released from 3-trifluoromethyl-quinoxaline 1,4-dioxides upon one-electron reduction by cytochrome P450 oxidoreductase. This process effectively competes with back oxidation of the intermediate radical anion by oxygen and underlies the increased aerobic cytotoxicity of such compounds compared to that seen for the related clinical bioreductive benzotriazine drug, tirapazamine.

Citation

Yadav, P., Marshall, A. J., Reynisson, J., Denny, W. A., Hay, M. P., & Anderson, R. F. (in press). Fragmentation of the quinoxaline N-oxide bond to the ˙OH radical upon one-electron bioreduction. Chemical Communications, 50(89), 13729-13731. https://doi.org/10.1039/c4cc05657d

• Journal Article Type: Article
• Acceptance Date: Sep 12, 2014
• Online Publication Date: Sep 18, 2014
• Deposit Date: Jun 9, 2023
• Journal: Chem. Commun.
• Print ISSN: 1359-7345
• Electronic ISSN: 1364-548X
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 50
• Issue: 89
• Pages: 13729-13731
• DOI: https://doi.org/10.1039/c4cc05657d
• Keywords: Materials Chemistry; Metals and Alloys; Surfaces, Coatings and Films; General Chemistry; Ceramics and Composites; Electronic, Optical and Magnetic Materials; Catalysis
• Additional Information: : This document is CrossCheck deposited; : Supplementary Information; : The Royal Society of Chemistry has an exclusive publication licence for this journal; OPEN ACCESS: The accepted version of this article will be made freely available after a 12 month embargo period; : Received 22 July 2014; Accepted 12 September 2014; Accepted Manuscript published 18 September 2014; Advance Article published 24 September 2014; Version of Record published 14 October 2014