Novel carboranes with a DNA binding unit for the treatment of cancer by boron neutron capture therapy

Chembiochem. 2002 Mar 1;3(2-3):219-25. doi: 10.1002/1439-7633(20020301)3:2/3<219::aid-cbic219>3.0.co;2-#.

Abstract

The synthesis and biological evaluation of two ortho-carborane derivatives which contain a 5,6,7-trimethoxyindole (TMI) unit for use in boron neutron capture therapy is described. The TMI moiety is known to be the DNA-binding part of the highly potent anticancer agent duocarmycin A. The ortho-carborane derivatives were prepared from amino alkynes which were bound to a protected TMI carboxylic acid. Addition of decaborane(14) to the alkyne triple bond with subsequent removal of the tert-butoxycarbonyl (Boc) and benzyl protecting groups gave the desired product. Boron uptake from the ortho-carborane derivatives into B-16 melanoma cells was higher and faster than that observed with L-p-boronophenylalanine (BPA), which is in use in the clinic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boranes / chemical synthesis
  • Boranes / metabolism
  • Boranes / pharmacology*
  • Boron Neutron Capture Therapy / methods*
  • Bronchial Neoplasms / genetics
  • Bronchial Neoplasms / metabolism
  • Bronchial Neoplasms / radiotherapy
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / radiotherapy
  • DNA, Neoplasm / metabolism*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / metabolism
  • Indoles / pharmacology*
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / radiotherapy
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / radiotherapy
  • Mice
  • Tumor Cells, Cultured

Substances

  • Boranes
  • DNA, Neoplasm
  • Indoles