Nucleoside conjugates V: Synthesis and biological activity of 9-(beta-D-arabinofuranosyl)adenine conjugates of corticosteroids.
Eight 5'-(steroid-21-phosphoryl)-9-(beta-D-arabinofuranosyl)-adenines (IV-XI) have been prepared and evaluated against L1210 lymphoid leukemia in culture. These include the 9-(beta-D-arabinofuranosyl)adenine conjugates of hydrocortisone (IV), cortisone (V), corticosterone (VI), cortexolone (VII), 11-deoxycorticosterone (VIII), prednisolone (IX), prednisone (X), and dexamethasone (XI). Conjugates IV, IX, X, and XI inhibited the in vitro growth of L1210 lymphoid leukemia cells by 50% (ED50) at a concentration of 2.3-7.8 microM, while 9-(beta-D-arabinofuranosyl)adenine (vidarabine, I) and its 5'-monophosphate (II) each showed ED50 value of 30 microM. All of the conjugates were enzymatically hydrolyzed to the corresponding steroid and II, the latter undergoing further hydrolysis to I, by phosphodiesterase I, 5'-nucleotidase, and acid phosphatase. However, these conjugates were resistant to hydrolysis by alkaline phosphatase and adenosine deaminase.
D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005938:Glucocorticoids / Q000138:chemical synthesis* / Q000494:pharmacology; D006868:Hydrolysis; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D000243:Adenosine Deaminase; D014740:Vidarabine