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

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

  • Org Lett. 2018 Dec 7;20(23):7400-7404. doi: 10.1021/acs.orglett.8b03035.
Zhiwei Wen 1,  Jufang Peng 1,  Paloma R Tuttle 1,  Yaou Ren 1,  Carol Garcia 1,  Dipra Debnath 2,  Sunny Rishi 2,  Cameron Hanson 2,  Samuel Ward 2,  Anil Kumar 2,  Yanfeng Liu 3,  Weixi Zhao 3,  Peter M Glazer 3,  Yuan Liu 1,  Michael D Sevilla 2,  Amitava Adhikary 2,  Stanislaw F Wnuk 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry , Florida International University , Miami , Florida 33199 , United States.
  • 2 Department of Chemistry , Oakland University , Rochester , Michigan 48309 , United States.
  • 3 Department of Therapeutic Radiology , Yale University School of Medicine , New Haven , Connecticut 06520 , United States.
PMID: 30457873 DOI: 10.1021/acs.orglett.8b03035
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.

Figures
Products