2'-O-Nitro-1-β-D-arabinofuranosylcytosine. A New Derivative of 1-β-D-Arabinofuranosylcytosine That Resists Enzymatic Deamination and Has Antileukemic Activity

Article abstract of DOI:10.1021/jm00356a032

To overcome the susceptibility of the anticancer drug 1-β-D-arabinofuranosylcytosine (ara-C) to enzymatic deamination, and hence deactivation, we prepared the 2'-O-nitro-1-β-D-arabinofuranosylcytosine (termed nitrara-C) and evaluated it for biological activity.Nitrara-C was resistant to enzymatic deamination and inhibited the proliferation of several strains of human leukemic T and B lymphoblasts grown in culture.Moreover, it substantially extended the life spans of mice with L1210 leukemia.Studies with ara-C-resistant human leukemic lymphoblasts deficient in deoxycytidine kinase activity disclosed that the inhibitory activity of the new compound depends on its phosphorylation.