Synthesis and in vitro evaluation of 5-closo- and 5-nido-orthocarboranyluridines as boron carriers

Sugar-part modified closo-carboranyluridines, 5-(o-carboran-1-yl)-2',3'-dideoxy-3'-thiauridine 5 and 5-(o-carboran-1-yl)-2',3'-dideoxy-2'alpha-phenylthiouridine 6, were synthesized. These newly synthesized closo-carboranyluridines, 5 and 6, and previously synthesized 5-(o-carboran-1-yl)uridine 1 were converted to the corresponding nido-carboranyluridines 18, 19, and 17, respectively. Water-solubility of nide-type 17 was about 100 times higher than that of its close-counterpart 1. Water-solubilities of sugar modified nido-types 18 and 19 were about 1000 times higher than those of their closo-counterparts 5 and 6. Cytotoxicities of the nido-types (17 and 19) were about 10 times lower than those of the corresponding close-counterparts (1 and 6, respectively). Cellular uptake of the nido-types (17 and 19) was in the level similar to that of the close-counterparts (1 and 6, respectively), although it is often believed that cellular uptake of hydrophilic carboranes (nido-forms) is much lower than that of lipophilic closo-carboranes.