Synthesis and in vitro evaluation of boronated uridine and glucose derivatives for boron neutron capture therapy

J Med Chem. 1992 May 1;35(9):1628-33. doi: 10.1021/jm00087a019.

Abstract

The following boron-containing nucleoside and glucose derivatives have been synthesized as potential boron delivery agents for boron neutron capture therapy (BNCT): 2'-O-(o-carboran-1-ylmethyl)uridine (4a), 3'-O-(o-carboran-1-ylmethyl)uridine (4b), sodium 7-(uridin-2'-ylmethyl)dodecahydro-7,8-dicarba-++ +nido-undecaborate (5), 5'-O-(o-carboran-1-ylmethyl)uridine (9), and 3'-O-(o-carboran-1-ylmethyl)-D-glucose (13). In vitro cellular uptake studies were performed with F98 rat glioma cells. Following 16 h incubation, cellular boron concentrations were determined by direct current plasma atomic emission spectroscopy (DCP-AES). Boron concentrations ranged from 65 to 103 micrograms/g of cells for the neutral closo structures compared with 1.5 micrograms/g of cells for the charged nido species. Cellular uptake of sodium mercaptoundecahydro-closo-dodecaborate (BSH), the compound currently being used in Japan for the treatment of malignant brain tumors by BNCT, was 2 micrograms/g of cells.

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
  • Boron*
  • Glioma / metabolism
  • Glioma / radiotherapy
  • Glucose / analogs & derivatives*
  • Glucose / chemical synthesis
  • Glucose / pharmacology
  • Neutrons*
  • Radiotherapy, High-Energy*
  • Rats
  • Tumor Cells, Cultured
  • Uridine / analogs & derivatives*
  • Uridine / chemical synthesis
  • Uridine / pharmacology

Substances

  • Glucose
  • Boron
  • Uridine