Nucleoside dimers analogs containing floxuridine and thymidine with unnatural linker groups: synthesis and cancer line studies. Part III

Nucleosides Nucleotides Nucleic Acids. 2019;38(12):980-1005. doi: 10.1080/15257770.2019.1641206. Epub 2019 Aug 5.

Abstract

Two series of novel fluorinated nucleosides dimers with an unnatural 1,2,3-triazole linkage were synthesized. The obtained molecules were prepared using "click" chemistry approach based on copper(I) catalyzed Huisgen azide-alkyne cycloaddition. It was performed between 3'- and 5'-azido-nucleosides as the azide components, and the 3'-O- and 5'-O-propargyl-nucleosides as the alkyne components. Based on analysis of the 3 JHH, 3 JH1'C2 and 3 JH1'C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. All described nucleosides dimers analogs were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7).

Keywords: KB and MCF-7; click chemistry; fluorinated nucleosides; heterodinucleotides; human cancer cell lines: HeLa.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Survival / drug effects
  • Click Chemistry / methods
  • Cycloaddition Reaction / methods
  • Dimerization
  • Floxuridine / chemistry*
  • HeLa Cells
  • Humans
  • KB Cells
  • MCF-7 Cells
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Nucleosides / chemical synthesis*
  • Nucleosides / pharmacology
  • Thymidine / chemistry*
  • Triazoles / chemistry*

Substances

  • Antineoplastic Agents
  • Nucleosides
  • Triazoles
  • Floxuridine
  • Thymidine