Cell metabolism of acyclovir phosphonate derivatives and antiherpesvirus activity of their combinations with alpha2-interferon.
The combinational use of acyclovir (ACV) phosphonate esters and alpha(2)-interferon was shown to produce a synergistic effect on inhibition of HSV-1 replication in Vero cell cultures. Unlike other acyclovir phosphonate derivatives studied earlier, ACV H-phosphonate is not an ACV prodrug. On penetrating into the cells, it may be directly converted into ACV monophosphate escaping dephosphonylation-phosphorylation steps.
Skoblov
Yuri S
YS
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov str., Moscow 119991, Russian Federation. ihba-imb@mail.ru
Karpenko
Inna L
IL
Jasko
Maxim V
MV
Kukhanova
Marina K
MK
Andronova
Valery L
VL
Galegov
Georgy A
GA
Sidorov
Georgy V
GV
Myasoedov
Nicolai F
NF
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002522:Chlorocebus aethiops; D002845:Chromatography / Q000379:methods; D015195:Drug Design; D006564:Herpesviridae / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D063065:Organophosphonates / Q000737:chemistry*; D010766:Phosphorylation; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry; D014709:Vero Cells
D000998:Antiviral Agents; D016898:Interferon-alpha; D063065:Organophosphonates; C026145:acyclovir monophosphate; D011683:Purine-Nucleoside Phosphorylase; D000212:Acyclovir