title: 5'-Hydrogenphosphonates of anti-HIV nucleoside analogues revisited: controversial mode of action.
abstract: The monomeric and symmetrical dimeric 5'-hydrogenphosphonate derivatives of AZT were prepared and evaluated for their inhibitory properties against HIV-1 in several cell lines. The synthesis of the compounds was achieved by reaction of AZT with in situ prepared phosphorus tris(imidazolide) or with phosphonic acid in the presence of pivaloyl chloride. The two title compounds showed in vitro anti-HIV activity similar to (but not better than) that of AZT in three cell lines which were not deficient in thymidine kinase. On the other hand they were inactive in CEM-TK- cells. Pharmacokinetic studies in several media corroborate the assumption that these compounds must not be considered as 'true antiviral agents', but that they act by releasing their nucleoside entity.
authors.affiliation: Laboratoire de Chimie Bioorganique, U.R.A. C.N.R.S. n. 488, Université de Montpellier II, Sciences et Techniques du Languedoc, Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Gosselin
authors.forename: C
authors.initials: C
authors.lastname: Périgaud
authors.forename: I
authors.initials: I
authors.lastname: Lefebvre
authors.forename: A
authors.initials: A
authors.lastname: Pompon
authors.forename: A M
authors.initials: AM
authors.lastname: Aubertin
authors.forename: A
authors.initials: A
authors.lastname: Kirn
authors.forename: T
authors.initials: T
authors.lastname: Szabo
authors.forename: J
authors.initials: J
authors.lastname: Stawinski
authors.forename: J L
authors.initials: JL
authors.lastname: Imbach
mesh_terms: D002460:Cell Line; D054306:Dideoxynucleotides; D004355:Drug Stability; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011355:Prodrugs / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D013942:Thymine Nucleotides / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D054306:Dideoxynucleotides; D011355:Prodrugs; D013942:Thymine Nucleotides; C057287:3'-azido-3'-deoxythymidine 5'phosphate; D015215:Zidovudine