Synthesis and antiviral and cytostatic properties of 3'-deoxy-3'-fluoro- and 2'-azido-3'-fluoro-2',3'-dideoxy-D-ribofuranosides of natural heterocyclic bases

J Med Chem. 1991 Jul;34(7):2195-202. doi: 10.1021/jm00111a040.

Abstract

A series of 3'-deoxy-3'-fluoro- and 2'-azido-2',3'-dideoxy-3'-fluoro-D-ribofuranosides of natural heterocyclic bases have been synthesized with the use of universal carbohydrate precursors, viz., 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-D-ribofuranose and methyl 2-azido-5-O-benzoyl-2,3-dideoxy-3-fluoro-beta-D-ribofuranoside, respectively. The cytostatic and antiviral activity of the compounds was evaluated against a variety of tumor cell lines and DNA/RNA viruses, respectively. As the most active compound, from both a cytostatic and antiviral activity viewpoint, emerged 3'-deoxy-3'-fluoroadenosine. It inhibited the proliferation of some tumor cell lines (i.e. murine leukemia L1210 and human T-lymphocyte MT-4) at a concentration of 0.2-2 micrograms/mL, and proved inhibitory to the replication of positive-stranded RNA viruses (i.e. polio, Coxsackie, Sindbis, Semliki forest), double-stranded RNA viruses (i.e. reo), and some DNA viruses (i.e. vaccinia) at a concentration of 1-4 micrograms/mL, which is well below the cytotoxicity threshold (40 micrograms/mL).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Cell Line
  • Chemical Phenomena
  • Chemistry
  • Chlorocebus aethiops
  • Dideoxynucleosides / chemical synthesis*
  • Dideoxynucleosides / pharmacology
  • Humans
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / pharmacology
  • Leukemia L1210 / drug therapy
  • Microbial Sensitivity Tests
  • Rabbits
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Dideoxynucleosides
  • Hydrocarbons, Fluorinated