title: Activity of the (R)-enantiomers of 9-(2-phosphonylmethoxypropyl)-adenine and 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine against human immunodeficiency virus in different human cell systems.
abstract: The (S)- and (R)-enantiomers of 9-(2-phosphonylmethoxypropyl) derivatives of adenine (PMPA) and 2,6-diaminopurine (PMPDAP) were evaluated for their inhibitory effect on HIV replication in several human cell systems, including natural peripheral blood lymphocytes (PBL) and freshly isolated monocyte/macrophages (M/M). The (R)-enantiomers of PMPDAP and PMPA were approximately 10-to-100-fold more effective against HIV than their (S)-enantiomeric counterparts. The antiviral efficacy of (R)-PMPA was comparable to that of the prototype acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The most potent and selective HIV inhibitor was (R)-PMPDAP. Its 50% effective concentration ranged from 0.01 microM for HIV-1/Ba-L in M/M to 1-2.8 microM for HIV-1/IIIB and HIV-1/HE in C8166, CEM, Molt/4, MT-4 and PBL cells. Both (R)-PMPA and (R)-PMPDAP were not toxic to the host cells at 300 microM.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: S
authors.initials: S
authors.lastname: Aquaro
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
authors.forename: M
authors.initials: M
authors.lastname: Witvrouw
authors.forename: A
authors.initials: A
authors.lastname: Holý
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D012999:Soman / Q000031:analogs & derivatives* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: C090125:9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine; D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C046573:pinacolyl methylphosphonic acid; C053001:adefovir; D012999:Soman; D000225:Adenine