title: The 2',3'-dideoxyriboside of 2,6-diaminopurine selectively inhibits human immunodeficiency virus (HIV) replication in vitro.
abstract: The 2',3'-dideoxyriboside of 2,6-diaminopurine(ddDAPR) is, like 2',3'-dideoxyadenosine (ddAdo), a potent and selective inhibitor of human immunodeficiency virus (HIV) in vitro. The ddDAPR compound inhibits HIV antigen expression and HIV-induced cytopathogenicity in MT4 cells at a 50% effective dose (ED50) of 2.5-3.6 microM, as compared to 3.1-6.4 microM for ddAdo. Both compounds are endowed with a high selectivity index: 112 for ddDAPR and 139 for ddAdo. The 2',3'-unsaturated derivatives of ddDAPR and ddAdo, i.e. ddeDAPR and ddeAdo, are considerably more cytotoxic and less effective against HIV than the parental compounds. Like ddAdo, ddDAPR is only weakly inhibitory to the proliferation and DNA and RNA synthesis of a series of human B-lymphoblast, T-lymphoblast and T-lymphocyte cell lines. In contrast to ddAdo, which is rapidly deaminated by beef intestine adenosine deaminase at an initial velocity (Vi) of 145 mumol/mg protein/min, ddDAPR and ddeDAPR are poor substrates for the enzyme (Vi: 8 and 0.7 mumol/mg protein/min, respectively), which further contributes to the potential of ddDAPR as a chemotherapeutic agent against AIDS.
mesh_terms: D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D004261:DNA Replication / Q000187:drug effects*; D003839:Deoxyadenosines / Q000031:analogs & derivatives* / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D015488:HIV Antigens; D006801:Humans; D014779:Virus Replication / Q000187:drug effects
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000956:Antigens, Viral; D000998:Antiviral Agents; D003839:Deoxyadenosines; D015488:HIV Antigens; C052692:2,6-diaminopurine 2',3'-dideoxyriboside; D016048:Dideoxyadenosine