Carborane-Appended Saccharides: Prime Candidates for Boron Neutron Capture Therapy (BNCT) Clinical Trials

Carborane-appended 5-thio-D- glucopyranose (TDG) and deoxyribose derivatives were synthesized and evaluated for accumulation in cancer cells, cytotoxicity, and efficacy in an in vitro boron neutron capture therapy (BNCT) assay. The nido- carborane-appended sugar conjugates were found to be less cytotoxic than their closo-carborane analogues. Biological evaluation with human hepatocellular carcinoma cells (SK-Hep1), bladder (T-24), and prostate (DU-145) cancer cells confirmed that the nido-carborane sugar conjugates were more effectively accumulated than the currently employed boronated agents used in clinical trials, namely boronophenylalanine (BPA) or sodium borocaptate (BSH). BNCT performed with nido- carborane-appended saccharides in a murine squamous cell carcinoma cell line (SCC-VII), indicated lower survival fraction for nido-carborane-appended TDG than that for BPA. These results provide justification for the further development and testing of carborane- appended saccharides for use in BNCT.