Lipophilic glycosyl phosphotriester derivatives of AZT: synthesis, NMR transmembrane transport study, and antiviral activity.
Phosphate derivatives of AZT esterified with a carbohydrate (D-glucose, D-mannose, and ethyl D-mannopyranoside) and a hexadecyl chain were prepared from glucose 6-phosphate and D-mannose precursors. The 31P NMR study of the mannosyl phosphotriester series in the presence of large unilamellar vesicles demonstrated either an interaction with the external lipid layer or a transmembrane transport into the intravesicular interface. The antiviral activity, measured by the inhibition of cytopathogenicity on different infected cells and of reverse transcriptase activity in the supernatant of cultures, appeared to be comparable to that of AZT, in the micromolar range.
Henin
Y
Y
Unité d'Oncologie Virale, URA CNRS 1157, Institut Pasteur, Paris, France.
Gouyette
C
C
Schwartz
O
O
Debouzy
J C
JC
Neumann
J M
JM
Huynh-Dinh
T
T
D000998:Antiviral Agents; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D054306:Dideoxynucleotides; D006031:Glycosylation; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013942:Thymine Nucleotides; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology
D000998:Antiviral Agents; D054306:Dideoxynucleotides; D009943:Organophosphorus Compounds; D013942:Thymine Nucleotides; C069653:2-(mannopyranosidyl)ethyl 3'-azido-3'-deoxy-5'-thymidinyl phosphate; C069651:6-glucopyranosyl 3'-azido-3'-deoxy-5'-thymidinyl phosphate; C069652:6-mannopyranosyl 3'-azido-3'-deoxy-5'-thymidinyl phosphate; D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase