Title: Electron-Mediated Aminyl and Iminyl Radicals from C5 Azido-Modified Pyrimidine Nucleosides Augment Radiation Damage to Cancer Cells.
Authors: Wen, Zhiwei; Peng, Jufang; Tuttle, Paloma R; Ren, Yaou; Garcia, Carol; Debnath, Dipra; Rishi, Sunny; Hanson, Cameron; Ward, Samuel; Kumar, Anil; Liu, Yanfeng; Zhao, Weixi; Glazer, Peter M; Liu, Yuan; Sevilla, Michael D; Adhikary, Amitava; Wnuk, Stanislaw F
Published In Org Lett, (2018 12 07)
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 π-aminyl radicals followed by facile conversion to σ-iminyl radicals either via a bimolecular reaction involving intermediate α-azidoalkyl radicals in AmdU/AmdC or by tautomerization in AvdU/AvdC. AmdU demonstrates effective radiosensitization in EMT6 tumor cells.
PubMed ID: 30457873
MeSH Terms: Cell Line, Tumor; Cell Survival/drug effects; Electrons*; Free Radicals/chemistry; Free Radicals/pharmacology; Humans; Molecular Structure; Pyrimidine Nucleosides/chemical synthesis; Pyrimidine Nucleosides/chemistry; Pyrimidine Nucleosides/pharmacology*