Synthesis and biological properties of 5-o-carboranyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil

J Med Chem. 1994 Aug 5;37(16):2583-8. doi: 10.1021/jm00042a011.

Abstract

A novel 5-o-carboranyl-containing nucleoside, 5-o-carboranyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (6, CFAU), was synthesized as a potential intracellular neutron capture agent. This compound was prepared in five steps starting from 5-iodo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (1). The desired carboranyl derivative was obtained by addition of decaborane [as the bis(propionitrile) adduct] to the protected acetylenic nucleoside precursor followed by debenzoylation. The synthesis of CFAU was also performed by glycosylation of the suitably protected 5-o-carboranyluracil with the appropriate 2-fluoroarabinosyl derivative. This compound was evaluated for its cytotoxicity in human lymphocytes, monkey cells, and rat and human gliomas cells, as well as for antiviral activity against human immunodeficiency virus and herpes simplex virus type 1. Its biological activity was compared to 5-o-carboranyl-1-(2-deoxyribofuranosyl)uracil in these cell culture systems, human bone marrow cells, and mice. The results obtained to date suggest that CFAU has suitable characteristics as a sensitizer for boron neutron capture therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Arabinofuranosyluracil / analogs & derivatives*
  • Arabinofuranosyluracil / chemical synthesis
  • Arabinofuranosyluracil / pharmacology
  • Arabinofuranosyluracil / toxicity
  • Bone Marrow / drug effects
  • Boron Compounds / chemical synthesis*
  • Boron Compounds / pharmacology
  • Boron Compounds / toxicity
  • Boron Neutron Capture Therapy*
  • Cell Survival / drug effects
  • Female
  • Glioma / pathology
  • Glycosylation
  • HIV-1 / drug effects
  • Herpesvirus 1, Human / drug effects
  • Humans
  • Lymphocytes / drug effects
  • Mice
  • Radiation-Sensitizing Agents / chemical synthesis*
  • Rats
  • Tumor Cells, Cultured

Substances

  • Antiviral Agents
  • Boron Compounds
  • Radiation-Sensitizing Agents
  • 5-o-carboranyl-1-(2-deoxy-2-fluoro-arabinofuranosyl)uracil
  • Arabinofuranosyluracil