Synthesis, susceptibility to enzymatic phosphorylation, cytotoxicity and in vitro antiviral activity of lipophilic pyrimidine nucleoside/carborane conjugates

Abstract

We synthesized a series of new uridine and 2′-deoxyuridine conjugates of the o-carborane cluster attached at C-5 through a linker comprising the ethynyl group and/or triazole ring separated by alkane chains. The obtained conjugates have low or medium toxicity and are phosphorylated moderately by nucleoside kinases TK1 and TK2 and efficiently by dCK. Low toxicity and susceptibility to phosphorylation makes them candidates for application as boron carriers for boron neutron capture therapy (BNCT), with compound 15 phosphorylated efficiently by all three enzymes as the best hit.