Characterisation of radicals formed by the triazine 1,4-dioxide hypoxia-activated prodrug, SN30000

Anderson, Robert F.; Yadav, Pooja; Patel, Deepa; Reynisson, Jóhannes; Tipparaju, Smitha R.; Guise, Christopher P.; Patterson, Adam V.; Denny, William A.; Maroz, Andrej; Shinde, Sujata S.; Hay, Michael P.

Abstract

The radical species underlying the activity of the bioreductive anticancer prodrug, SN30000, have been identified by electron paramagnetic resonance and pulse radiolysis techniques. Spin-trapping experiments indicate both an aryl-type radical and an oxidising radical, trapped as a carbon-centred radical, are formed from the protonated radical anion of SN30000. The carbon-centred radical, produced upon the one-electron oxidation of the 2-electron reduced metabolite of SN30000, oxidises 2-deoxyribose, a model for the site of damage on DNA which leads to double strand breaks. Calculations using density functional theory support the assignments made.

Citation

Anderson, R. F., Yadav, P., Patel, D., Reynisson, J., Tipparaju, S. R., Guise, C. P., Patterson, A. V., Denny, W. A., Maroz, A., Shinde, S. S., & Hay, M. P. (in press). Characterisation of radicals formed by the triazine 1,4-dioxide hypoxia-activated prodrug, SN30000. Organic and Biomolecular Chemistry, 12(21), 3386-3392. https://doi.org/10.1039/c4ob00236a

• Journal Article Type: Article
• Acceptance Date: Apr 9, 2014
• Online Publication Date: Apr 10, 2014
• Deposit Date: Jun 8, 2023
• Journal: Org. Biomol. Chem.
• Print ISSN: 1477-0520
• Electronic ISSN: 1477-0539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 21
• Pages: 3386-3392
• DOI: https://doi.org/10.1039/c4ob00236a
• Keywords: Organic Chemistry; Physical and Theoretical Chemistry; Biochemistry
• Public URL: https://keele-repository.worktribe.com/output/443389
• 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 31 January 2014; Accepted 9 April 2014; Accepted Manuscript published 10 April 2014; Advance Article published 16 April 2014; Version of Record published 7 May 2014