title: Marked in vivo antiretrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine, a selective anti-human immunodeficiency virus agent.
abstract: 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective inhibitor of the replication of human immunodeficiency virus (HIV) in vitro in human T-lymphocyte MT-4, H9, and ATH8 cells. PMEA also inhibits Moloney murine sarcoma virus (Mo-MSV)-induced transformation of murine C3H embryo fibroblasts. Moreover, PMEA causes a dose-dependent suppression of tumor formation and associated mortality in mice inoculated with Mo-MSV. At a dose of 50 or 20 mg/kg per day PMEA effected a 90-100% protection of the mice against Mo-MSV-induced tumor formation and mortality. Even with a PMEA dose as low as 1 to 5 mg/kg per day, tumor formation was significantly delayed and the survival rate was significantly enhanced. In parallel experiments, azidothymidine exhibited a comparable inhibitory effect on Mo-MSV-induced tumor formation and associated death only at a 25-fold higher dose than PMEA. Because PMEA has stronger in vivo antiretrovirus potency and selectivity than azidothymidine and various other compounds currently being subjected to clinical trials, PMEA studies should be pursued to assess the potential of this compound in the treatment of acquired immunodeficiency syndrome (AIDS) and other retrovirus infections in humans.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: L
authors.initials: L
authors.lastname: Naesens
authors.forename: P
authors.initials: P
authors.lastname: Herdewijn
authors.forename: I
authors.initials: I
authors.lastname: Rosenberg
authors.forename: A
authors.initials: A
authors.lastname: Holy
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: D G
authors.initials: DG
authors.lastname: Johns
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D008815:Mice, Inbred Strains; D008980:Moloney murine sarcoma virus / Q000187:drug effects / Q000235:genetics; D063065:Organophosphonates; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine