Synthesis and biological evaluation of nucleobase-modified analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd).

A series of nucleobase-modified analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd) were designed to overcome the strict substrate specificity of the activating uridine-cytidine kinase. EUrd, ECyd and target nucleosides were obtained using a short convergent synthetic route utilizing diacetone-alpha-D-glucose as starting material. 5-Iodo-substituted EUrd was the most potent inhibitor among the novel nucleobase-modified analogs in in vitro assays against human adenocarcinoma breast and prostate cancer cells with IC50 values down to 35 nM.