Synthesis and in vitro evaluation of boronated uridine and glucose derivatives for boron neutron capture therapy

Article abstract of DOI:10.1021/jm00087a019

The following boron-containing nucleoside and glucose derivatives have been synthesized as potential boron delivery agents for boron neutron capture therapy (BNCT): 2'-O(o-carboran-1-ylmethyl)uridine (4a), 3'-O-(o-carboran-1- ylmethyl)uridine (4b), sodium 7-(uridin-2'-ylmethyl)dodecahydro-7,8-dicarba- nido-undecaborate (5), 5'-O-(o-carboran-1-ylmethyl)uridine (9), and 3'-O-(o- carboran-1-ylmethyl)-D-glucose (13). In vitro cellular uptake studies were performed with F98 rat glioma cells. Following 16 h incubation, cellular boron concentrations were determined by direct current plasma atomic emission spectroscopy (DCP-AES). Boron concentrations ranged from 65 to 103 μg/g of cells for the neutral closo structures compared with 1.5 μg/g of cells for the charged nido species. Cellular uptake of sodium mercaptoundecahydro- closo-dodecaborate (BSH), the compound currently being used in Japan for the treatment of malignant brain tumors by BNCT, was 2 μg/g of cells.