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

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

doi:10.1039/c4ob00236a

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

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

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

22 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3386-3392
Number of pages	7
Journal	Organic and Biomolecular Chemistry
Volume	12
Issue number	21
DOIs	https://doi.org/10.1039/c4ob00236a
Publication status	Published - 7 Jun 2014
Externally published	Yes

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

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.",

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AU - Anderson, Robert F.

AU - Yadav, Pooja

AU - Patel, Deepa

AU - Reynisson, Jóhannes

AU - Tipparaju, Smitha R.

AU - Guise, Christopher P.

AU - Patterson, Adam V.

AU - Denny, William A.

AU - Maroz, Andrej

AU - Shinde, Sujata S.

AU - Hay, Michael P.

PY - 2014/6/7

Y1 - 2014/6/7

N2 - 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.

AB - 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.

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JO - Organic and Biomolecular Chemistry

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ER -

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

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