Remarkable Enhancement in Boron Uptake Within Glioblastoma Cells With Carboranyl–Indole Carboxamides

Abstract

Novelb oron-rich, carboranyl-indolec arboxamide ligands were prepared and found to effectively target the 18 kDa translocator protein (TSPO), an upregulated mitochondrial membrane-bound protein which has been observed in variety of tumor cell lines and its expression appears to be proportionalt ot he degree of tumorigenicity, emphasizing ak ey role in cancer cell proliferation.B oth boronated compounds displayed remarkably high affinities for the TSPO. In addition, the in vitro uptake of these compoundsi nto T98G human glioma cells was found to be 25to 100-fold greater than that of clinical boron neutron capture therapy (BNCT) agents.

Adventures in Translocation: Studies of the Translocator Protein (TSPO) 18 kDa

“…A follow-up study reported two carborane-containing indole carboxamide TSPO ligands with even better uptake and toxicity profiles; plans for in vivo studies are currently in the pipeline. [48] Over the years, we have also reported on the synthesis of TSPO ligands not based on the pyrazolopyrimidine scaffold. Taking inspiration from a 1996 study by Campiani and co-workers, [49] we synthesised a library of 10 pyrrolobenzoxazepines to better understand their binding and functional properties at TSPO through systematic in vitro investigations (structures of three of these compounds that are shown in Fig.…”

Dodecaborate Conjugates Targeting Tumor Cell Overexpressing Translocator Protein for Boron Neutron Capture Therapy

“…In BNCT, TSPO is a potential target for tumor targeting, and several carborane-containing TSPO ligands have been reported. , Carborane has been used as a boron source for BNCT, because of its high boron content and ease of organic moiety conjugation via c-c bonds using carbon atoms contained within the boron cluster structure. , However, carborane exhibits very high toxicity and very low water solubility, and carborane based compounds are not used in clinical studies.…”