Novel Carboranes with a DNA Binding Unit for the Treatment of Cancer by Boron Neutron Capture Therapy

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.