Synthesis and biological activity of novel N⁶-substituted and 2,N⁶-disubstituted adenine ribo- and 3′-C-methyl- ribonucleosides as antitumor agents

A series of N⁶-aminopurine-9-β-d-ribonucleosides and ribose-modified 3′-C-methyl analogues substituted at N⁶- position with a small group like hydroxy, methoxy or amino group or at C2(N ⁶) position have been synthesized and tested against a panel of human leukemia and carcinoma cell lines. N⁶-Hydrazino-9-β-d- ribofuranosyl-purine (5) displayed the best antiproliferative activity in the low micromolar or submicromolar range against all tested tumor cell lines. The activity of this nucleoside is related in part to ribonucleotide reductase inhibition. C2-modification or 3′-C-methylation in N⁶- substituted adenosine analogues leads to a decrease or loss in activity.