Novel carboranes with a DNA binding unit for the treatment of cancer by boron neutron capture therapy.
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.
Tietze
Lutz F
LF
Institut für Organische, Chemie Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany. ltietze@gwdg.de
Griesbach
Ulrich
U
Bothe
Ulrich
U
Nakamura
Hiroyuki
H
Yamamoto
Yoshinori
Y
D000818:Animals; D001880:Boranes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001984:Bronchial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D004273:DNA, Neoplasm / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D051379:Mice; D014407:Tumor Cells, Cultured
D001880:Boranes; D004273:DNA, Neoplasm; D007211:Indoles