title: Synthesis and biological evaluation of nucleobase-modified analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd).
abstract: 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.
authors.affiliation: Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hrdlicka
authors.forename: Jan S
authors.initials: JS
authors.lastname: Jepsen
authors.forename: Claus
authors.initials: C
authors.lastname: Nielsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; C103085:1-(3-C-ethynylribopentofuranosyl)uracil; D000970:Antineoplastic Agents; D003562:Cytidine; D014529:Uridine