Synthesis and cytotoxic activity of 6-vinyl- and 6-ethynyluridine and 8-vinyl-and 8-ethynyladenosine.
It is well-known that the introduction of vinyl and ethynyl moieties into nucleosides is of crucial importance for cytostatic, antiviral, or other biological activities. In this study 6- and 8-vinyl-and -ethynyluridine and -adenosine were prepared by a general procedure involving the palladium-catalyzed cross-coupling of trimethylsilylacetylene or vinyltributyltin. The introduction of a vinyl group at C-6 of uridine or an ethynyl group at C-8 of adenosine resulted in nucleoside derivatives showing cytostatic activity against several murine and/or human tumor cell lines. Interestingly, 8-vinyladenosine had pronounced selective inhibitory effects on human (Molt/4F and MT-4) versus murine (L1210 and FM3A) tumor cell lines.
Departimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
S
S
Manfredini
P G
PG
Baraldi
R
R
Bazzanini
M
M
Marangoni
D
D
Simoni
J
J
Balzarini
E
E
De Clercq
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D017646:Organosilicon Compounds / Q000138:chemical synthesis* / Q000633:toxicity*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity*; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000633:toxicity*
D000970:Antineoplastic Agents; D017646:Organosilicon Compounds; D014753:Vinyl Compounds; D000241:Adenosine; D014529:Uridine