title: Phosphate derivatives of AZT display enhanced selectivity of action against HIV 1 by comparison to the parent nucleoside.
abstract: Novel phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. In particular, phosphates carrying ester-containing side-chains are described. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity. In several cases the phosphate derivatives are more selective in their action than the parent nucleoside AZT. In particular, this arises from the low toxicity of the phosphate pro-drugs by comparison to AZT. These data support the suggestion that the phosphate derivatives exert their biological effects via intracellular release of the nucleotide forms, and suggests that such pro-drug forms may be worthy of further study.
authors.affiliation: Department of Chemistry, University of Southampton, Highfield, UK.
authors.forename: C
authors.initials: C
authors.lastname: McGuigan
authors.forename: C
authors.initials: C
authors.lastname: Nickson
authors.forename: J
authors.initials: J
authors.lastname: Petrik
authors.forename: A
authors.initials: A
authors.lastname: Karpas
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D009943:Organophosphorus Compounds; D011355:Prodrugs; D015215:Zidovudine