Synthesis, structural characterization and biological evaluation of 4'-C-methyl- and phenyl-dioxolane pyrimidine and purine nucleosides

Arch Pharm Res. 2017 May;40(5):537-549. doi: 10.1007/s12272-016-0825-6. Epub 2016 Sep 11.

Abstract

Nucleoside analogues play an important role in antiviral, antibacterial and antineoplastic chemotherapy. Herein we report the synthesis, structural characterization and biological activity of some 4'-C -methyl- and -phenyl dioxolane-based nucleosides. In particular, α and β anomers of all natural nucleosides were obtained and characterized by NMR, HR-MS and X-ray crystallography. The compounds were tested for antimicrobial activity against some representative human pathogenic fungi, bacteria and viruses. Antitumor activity was evaluated in a large variety of human cancer cell-lines. Although most of the compounds showed non-significant activity, 23α weakly inhibited HIV-1 multiplication. Moreover, 22α and 32α demonstrated a residual antineoplastic activity, interestingly linked to the unnatural α configuration. These results may provide structural insights for the design of active antiviral and antitumor agents.

Keywords: 1,3-Dioxolanes; Antitumor; Antiviral; Nucleosides; Purines; Pyrimidines; Vorbrüggen reaction.

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Dioxolanes / chemical synthesis
  • Dioxolanes / chemistry
  • Dioxolanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HIV-1 / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Purine Nucleosides / chemical synthesis
  • Purine Nucleosides / chemistry
  • Purine Nucleosides / pharmacology*
  • Pyrimidine Nucleosides / chemical synthesis
  • Pyrimidine Nucleosides / chemistry
  • Pyrimidine Nucleosides / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Antineoplastic Agents
  • Dioxolanes
  • Purine Nucleosides
  • Pyrimidine Nucleosides
  • formal glycol