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.