Synthesis and biological evaluation of branched and conformationally restricted analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd).
The synthesis of branched and conformationally restricted analogs of the anticancer nucleosides 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd) is presented. Molecular modeling and (1)H NMR coupling constant analysis revealed that the furanose rings of all analogs except the LNA analog are conformationally biased towards South conformation, and are thus mimicking the structure of ECyd. All target nucleosides were devoid of anti-HIV or anticancer activity.
Hrdlicka
Patrick J
PJ
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK-5230 Odense M, Denmark.
Andersen
Nicolai K
NK
Jepsen
Jan S
JS
Hansen
Flemming G
FG
Haselmann
Kim F
KF
Nielsen
Claus
C
Wengel
Jesper
J
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D003562:Cytidine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D009690:Nucleic Acid Conformation; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D003562:Cytidine; D014529:Uridine