Synthesis, equilibrium, and biological study of a C-7 glucose boronic acid derivative as a potential candidate for boron neutron capture therapy

Bioorg Med Chem. 2022 Apr 1:59:116659. doi: 10.1016/j.bmc.2022.116659. Epub 2022 Feb 19.

Abstract

The synthesis of d-glucoheptose derivative containing a boronic moiety is described herein. Starting from benzyl 6,7-dideoxy-2,3,4-tri-O-benzyl-β-d-gluco-ept-6-enopyranoside, the introduction of the boronic acid was performed through a metathesis reaction by using MIDA vinyl boronic acid and the 2nd generation Grubbs catalyst. Hydrogenation led to the final product in only two reaction steps. This new sugar-containing boronic acid in the skeleton could mimic carbohydrate behavior and follow the glucose uptake in living cells. The in vitro toxicity tests performed in fibroblasts and glioma tumor cell lines showed minimal toxicity. Boron uptake measured using ICP-MS was minimal in fibroblasts, while in glioma cells showed a value of 6 ng of total boron accumulation per mg of cells, implying that compound 1a is able to accumulate selectively in the tumor tissues compared to normal.

Keywords: Boron Neutron Capture Therapy (BNCT); Boron uptake; Boronic acid; Carbohydrates; Cellular uptake; Metathesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron / pharmacology
  • Boron Compounds / pharmacology
  • Boron Neutron Capture Therapy*
  • Boronic Acids / pharmacology
  • Carbohydrates
  • Cell Line, Tumor
  • Glioma* / metabolism
  • Glucose
  • Humans

Substances

  • Boron Compounds
  • Boronic Acids
  • Carbohydrates
  • Glucose
  • Boron