Carborane-Containing Folic Acid bis-Amides: Synthesis and In Vitro Evaluation of Novel Promising Agents for Boron Delivery to Tumour Cells

Int J Mol Sci. 2022 Nov 8;23(22):13726. doi: 10.3390/ijms232213726.

Abstract

The design of highly selective low-toxic, low-molecular weight agents for boron delivery to tumour cells is of decisive importance for the development of boron neutron capture therapy (BNCT), a modern efficient combined method for cancer treatment. In this work, we developed a simple method for the preparation of new closo- and nido-carborane-containing folic acid bis-amides containing 18-20 boron atoms per molecule. Folic acid derivatives containing nido-carborane residues were characterised by high water solubility, low cytotoxicity, and demonstrated a good ability to deliver boron to tumour cells in in vitro experiments (up to 7.0 µg B/106 cells in the case of U87 MG human glioblastoma cells). The results obtained demonstrate the high potential of folic acid-nido-carborane conjugates as boron delivery agents to tumour cells for application in BNCT.

Keywords: BNCT; MTT assay; amides; boron accumulation; carboranes; cytotoxicity; folic acid; tumour cells.

MeSH terms

  • Amides
  • Boron* / pharmacology
  • Folic Acid / pharmacology
  • Glioblastoma*
  • Humans
  • Thinness

Substances

  • Boron
  • nido-carborane
  • Amides
  • Folic Acid