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Electron-Mediated Aminyl and Iminyl Radicals from C5 Azido-Modified Pyrimidine Nucleosides Augment Radiation Damage to Cancer Cells.

ABSTRACT: Two classes of azido-modified pyrimidine nucleosides were synthesized as potential radiosensitizers; one class is 5-azidomethyl-2'-deoxyuridine (AmdU) and cytidine (AmdC), while the second class is 5-(1-azidovinyl)-2'-deoxyuridine (AvdU) and cytidine (AvdC). The addition of radiation-produced electrons to C5-azido nucleosides leads to the formation of ?-aminyl radicals followed by facile conversion to ?-iminyl radicals either via a bimolecular reaction involving intermediate ?-azidoalkyl radicals in AmdU/AmdC or by tautomerization in AvdU/AvdC. AmdU demonstrates effective radiosensitization in EMT6 tumor cells.

SUBMITTER: Wen Z

PROVIDER: S-EPMC6465127 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Electron-Mediated Aminyl and Iminyl Radicals from C5 Azido-Modified Pyrimidine Nucleosides Augment Radiation Damage to Cancer Cells.

Wen Zhiwei Z Peng Jufang J Tuttle Paloma R PR Ren Yaou Y Garcia Carol C Debnath Dipra D Rishi Sunny S Hanson Cameron C Ward Samuel S Kumar Anil A Liu Yanfeng Y Zhao Weixi W Glazer Peter M PM Liu Yuan Y Sevilla Michael D MD Adhikary Amitava A Wnuk Stanislaw F SF

Organic letters 20181120 23

Two classes of azido-modified pyrimidine nucleosides were synthesized as potential radiosensitizers; one class is 5-azidomethyl-2'-deoxyuridine (AmdU) and cytidine (AmdC), while the second class is 5-(1-azidovinyl)-2'-deoxyuridine (AvdU) and cytidine (AvdC). The addition of radiation-produced electrons to C5-azido nucleosides leads to the formation of π-aminyl radicals followed by facile conversion to σ-iminyl radicals either via a bimolecular reaction involving intermediate α-azidoalkyl radical ...[more]

PMID: 30457873

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