title: S-acyl-2-thioethyl aryl phosphotriester derivatives of AZT: synthesis, antiviral activity, and stability study.
abstract: The synthesis, antiviral activity, and stability study of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing modified l-tyrosinyl residues are reported. These compounds were obtained via phosphoramidite (P(III)) chemistry from the appropriate aryl precursors. All the derivatives were evaluated for their in vitro anti-HIV activity, and they appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments, with EC(50) values between the micro- and nanomolar range, especially in thymidine kinase deficient (TK(-)) cells, showing their ability to act as mononucleotide prodrugs. The proposed decomposition process of these mixed mononucleoside aryl phosphotriesters successively involves an esterase and a phosphodiesterase hydrolysis.
authors.affiliation: UMR 5625 CNRS-UMII, Université Montpellier II, Case Courrier 008, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Peyrottes
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Coussot
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lefebvre
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Imbach
authors.forename: Gilles
authors.initials: G
authors.lastname: Gosselin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Aubertin
authors.forename: Christian
authors.initials: C
authors.lastname: Périgaud
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002457:Cell Extracts; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D010755:Organophosphates / Q000138:chemical synthesis* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013440:Sulfides / Q000138:chemical synthesis* / Q000494:pharmacology; D014779:Virus Replication; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D002457:Cell Extracts; D010755:Organophosphates; D013440:Sulfides; D015215:Zidovudine