title: Activity of acyclic nucleoside phosphonate analogues against human immunodeficiency virus in monocyte/macrophages and peripheral blood lymphocytes.
abstract: A number of acyclic nucleoside phosphonate analogues, including 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and its 2,6-diaminopurine derivative PMEDAP, (R,S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine [(R,S)-FPMPA] and its 2,6-diaminopurine derivative (R,S)-FPMPDAP were evaluated for their inhibitory effects on HIV-1 replication in two natural human cell systems, i.e. peripheral blood lymphocytes (PBL) and freshly prepared monocyte/macrophages (M/M). All compounds were potent inhibitors of HIV-1 replication in PBL [50% effective concentration (EC50): 0.94-3.9 microM] and M/M (EC50: 0.022-0.95 microM). In particular, (R,S)-FPMPA and (R,S)-FPMPDAP showed a greater antiviral selectivity than PMEA and PMEDAP due to the virtual lack of toxicity of the former compounds in these cell systems. Also, the antiviral selectivity of the acyclic nucleoside phosphonate analogues was much higher in M/M than in the human T-cell lines MT-4, ATH8 and CEM.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
authors.forename: D
authors.initials: D
authors.lastname: Schols
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000382:microbiology*; D008264:Macrophages / Q000382:microbiology*; D009000:Monocytes / Q000382:microbiology*; D009705:Nucleosides / Q000494:pharmacology*; D063065:Organophosphonates / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates