1. Novel carboranes with a DNA binding unit for the treatment of cancer by boron neutron capture therapy
- Author
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Tietze, LF, Griesbach, U, Bothe, U, Nakamura, Hiroyuki, and Yamamoto, Y
- Subjects
inorganic chemicals ,Indoles ,Carboxylic acid ,Melanoma, Experimental ,Alkyne ,chemistry.chemical_element ,Boron Neutron Capture Therapy ,Biochemistry ,Mice ,chemistry.chemical_compound ,Tumor Cells, Cultured ,Animals ,Humans ,Organic chemistry ,Moiety ,A-DNA ,Boranes ,Boron ,Melanoma ,Molecular Biology ,Duocarmycin ,chemistry.chemical_classification ,Bronchial Neoplasms ,Carcinoma ,Organic Chemistry ,DNA, Neoplasm ,Triple bond ,Combinatorial chemistry ,3. Good health ,chemistry ,Decaborane ,Molecular Medicine - 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.
- Published
- 2002