title: Nucleoside conjugates as potential antitumor agents. 2. Synthesis and biological activity of 1-(beta-D-arabinofuranosyl)cytosine conjugates of prednisolone and prednisone.
abstract: Two of the new anticancer drugs recently synthesized in our laboratory from conjugation of ara-C2 and several corticosteroids linked through a phosphodiester bond include prednisolone- (I) and prednisone-p-ara-C (II). They were demonstrated to be enzymatically hydrolyzed to the corresponding steroid and ara-CMP and the latter was further shown to be hydrolyzed to ara-C by phosphodiesterase I, snake venom, 5'-nucleotidase, and acid phosphatase. However, the conjugates were shown to be resistant to hydrolysis by alkaline phosphatase. The activity of conjugates I and II against L1210 lymphoid leukemia in female mice (C3D2F1/J) was significantly greater than that of ara-C alone or in combination with the steroid. In fact, when the optimum dosage of 75 (mumol/kg)/day x 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. However, when the conjugates were used, the ILS values were 89 and 100% respectively. These findings seem promising and have provided the bases for continued study of these new compounds.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D000882:Haplorhini; D006868:Hydrolysis; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D010215:Papio; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011241:Prednisone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D011239:Prednisolone; D011241:Prednisone