title: Activities of masked 2',3'-dideoxynucleoside monophosphate derivatives against human immunodeficiency virus in resting macrophages.
abstract: The anti-human immunodeficiency virus (HIV) activity of aryloxyphosphoramidate protides of a number of anti-HIV nucleoside analogues was assessed in resting primary monocyte-macrophages (M/M). While 2',3'-dideoxythymidine (d4T), 2',3'-dideoxyadenosine (ddA), and 2',3'-dideoxy-2',3'-didehydroadenosine (d4A) protides showed an anti-HIV activity that was 25- to 625-fold greater than the parent nucleotides d4T, ddA, and d4A, respectively, other aryloxyphosphoramidate protides showed similar or even lower anti-HIV activities than their parent compounds. This variable anti-HIV effect is most likely related to the different dynamics of intracellular nucleoside monophosphate release from the protides. Our results indicate the potential advantage of therapeutic use of this approach for some nucleotide analogues to affect HIV replication in M/M, one of the major reservoirs of HIV in vivo.
authors.affiliation: Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Aquaro
authors.forename: O
authors.initials: O
authors.lastname: Wedgwood
authors.forename: C
authors.initials: C
authors.lastname: Yarnold
authors.forename: D
authors.initials: D
authors.lastname: Cahard
authors.forename: R
authors.initials: R
authors.lastname: Pathinara
authors.forename: C
authors.initials: C
authors.lastname: McGuigan
authors.forename: R
authors.initials: R
authors.lastname: Calio'
authors.forename: E
authors.initials: E
authors.lastname: de Clercq
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D016048:Dideoxyadenosine / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; C019336:2',3'-dideoxythymidine; D016048:Dideoxyadenosine