Nucleoside conjugates as potential antitumor agents. 2. Synthesis and biological activity of 1-.beta.-D-arabinofuranosylcytosine conjugates of prednisolone and prednisone

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Abstract
Two of the new anticancer drugs recently synthesized from conjugation of ara-C [1-(.beta.-D-arabinofuranosyl)cytosine] and several corticosteroids linked through a phosphodiester bond include prednisolone- and prednisone-p-ara-C. They were enzymatically hydrolyzed to the corresponding steroid and ara-CMP and the latter was hydrolyzed to ara-C by phosphodiesterase I, snake venom, 5''-nucleotidase and acid phosphatase. The conjugates were resistant to hydrolysis by alkaline phosphatase. The activity of the conjugates against L1210 lymphoid leukemia in female mice (C3D2F1/J) was significantly greater than that of ara-C alone or in combination with the steroid. When the optimum dosage of 75 (.mu.mol/kg)/day .times. 5 was used, the administration of ara-C alone was followed by an increased life span (ILS) of 45%. This result is similar to that previously reported. With the same equimolar doses of mixtures of ara-C and either prednisolone or prednisone, the ILS values were 40 and 44%, respectively. When the conjugates were used, the ILS values were 89 and 100%, respectively. These findings seem promising and provide the basis for continued study of these new compounds.

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