Synthesis and biological activity of 5-phenylselenenyl-substituted pyrimidine nucleosides.
Several 5-phenylselenenyl derivatives of pyrimidine nucleosides were synthesized by electrophilic addition of phenylselenenyl chloride to the nucleosides under basic conditions. With use of this route, 5-(phenylselenenyl)-6-azauracil was also prepared. These compounds may serve as inhibitors of thymidylate synthase, as potential antiviral and anticancer agents, and as versatile intermediates for the synthesis of 5- or 6-substituted nucleosides. 5-(Phenylselenenyl)arabinosyluracil (PSAU, 4) and the corresponding cytosine analogue (PSAC, 5) were poor inhibitors of a promyelocytic leukemia cell line that was arabinosylcytosine-resistant. PSAU and PSAC were significantly less active than ara-C against L1210 cells and were found to selectively interfere with the cellular uptake and/or phosphorylation of 2'-deoxycytidine and 2'-deoxyuridine in intact L1210 cells.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D012510:Sarcoma 180 / Q000188:drug therapy; D012643:Selenium; D018139:Simplexvirus / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000964:Antimetabolites, Antineoplastic; D000998:Antiviral Agents; D007202:Indicators and Reagents; D011741:Pyrimidine Nucleosides; D012643:Selenium