Nucleoside conjugates V: Synthesis and biological activity of 9-(β-D-arabinofuranosyl)adenine conjugates of corticosteroids

Article abstract of DOI:10.1002/jps.2600730238

Eight 5'-(steroid-21-phosphoryl)-9-(β-D-arabinofuranosyl)adenines (IV-XI) have been prepared and evaluated against L1210 lymphoid leukemia in culture. These include the 9-(β-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 μM, while 9-(β-D-arabinofuranosyl)adenine (vidarabine, I) and its 5'-monophosphate (II) each showed ED₅₀ value of 30 μM. 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.