The antitumor activity of certain substituted nucleosides.
Tests were made of the antitumor activity against lymphoid leukemic L 5178 Y cells in vitro, as exhibited by the following compounds: 2'-O-methyl-araC, 5'-0-methyl-araC, N4,2'-O-dimethyl-araC, N4-methyl-araC, 2,2'-anhydro-5'-O-methyl-araC, N4-methyl-2,2'-anhydro-araC, 4-thio-2,2'-anhydro-araU and 5-amino-araU being a new analogue or araC. The synthesis of the latter compound is described. The activity of 5-amino-araU was tested also in vivo against L 1210 mouse leukemia. O'-Alkylation, N4-exo-alkylation and the change in the amino group position from 4 to 5 abolishes the susceptibility of the above analogues to cytidine deaminase but at the same time it substantially reduces their cytotoxic activity. It was shown that 5-ethyl-2'-deoxyuridine inhibits 14 and 26% in vitro the growth of L 5178 Y cells at concentrations 10(-6) and 10(-5) M, respectively. The possible biological significance of the latter compound is discussed.
D000818:Animals; D000970:Antineoplastic Agents; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009705:Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009705:Nucleosides; D003564:Cytidine Deaminase