Antitumor and Antiviral Activity of N6-Hydroxyadenine Nucleosides and Related Derivatives

摘要: ABSTRACT The first member of the series, N6-hydroxyadenosine (HAPR), exerted an antitumor activity in mouse leukemias and underwent clinical trials. A toxicity was observed, due to enzymatic hydrolysis by adenosine deaminase. 9-β-D-Arabinosyl-N6-hydroxyadenine (ara-HA) had inhibitory effect herpes simplex virus type 1 (HSV-1) replication, but it also toxic. 6-nitroso purine nucleosides ribosyl arabinosyl series were obtained oxidation corresponding N6-hydroxyadenine (HAP) derivatives. Nitrosation led N6-(nitroso)hydroxyamino derivative which, contrast its base, inactive. 9-3-D-ribofuranosyl-N6-(1-methylhydrazino) or N6-methylaminopurine gave N6-(methylnitroso)adenosine which growth leukemia. use deaminase inhibitors, erythro-9(2-hydroxy-3-nonyl)-adenine (EHNA) 2′-deoxycoformycin (2′-DCF) resulted increased antiviral N6-hydroxyadenines, they ineffective blocking toxic effects primates. These results prompted study new derivatives with substituents at C-2, as is known that 2-substituted adenosines are resistant attack. In fact, 2-amino (AHAPR) 2-fluoro (FHAPR) N6-hydroxyadenosines less affected than unsubstituted nucleosides. N2,N6-dihydroxyaminopurine ribonucleoside (DHAPR) effective against leukemia colon 38 tumor. All these potent anti-HSV-1 vitro. biological depends on their structure, being more those N-OH function nucleus.