Synthesis and in Vitro Evaluation of 5-<i>closo</i>- and 5-<i>nido</i>-Orthocarboranyluridines as Boron Carriers

Abstract

Abstract 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′α-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 nido-type 17 was about 100 times higher than that of its closo-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 closo-counterparts (1 and 6, respectively). Cellular uptake of the nido-types (17 and 19) was in the level similar to that of the closo-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.