RESUMO
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.
Assuntos
Aciclovir/análogos & derivados , Antivirais/farmacologia , Química Farmacêutica/métodos , Herpesviridae/metabolismo , Interferon-alfa/metabolismo , Organofosfonatos/química , Aciclovir/química , Animais , Antivirais/química , Chlorocebus aethiops , Cromatografia/métodos , Desenho de Fármacos , Cinética , Modelos Biológicos , Fosforilação , Purina-Núcleosídeo Fosforilase/química , Células VeroRESUMO
Phosphonate derivatives of acyclovir containing phosphorous acid and ethoxycarbonylphosphonic acid residues as well as their isopropyl esters were prepared. They selectively inhibited the herpes simplex virus 1 reproduction in Vero cell culture, the efficacy of esters being 3-4 times higher than that of ACV. The hydrolysis of the synthesized compounds was studied in the PBS buffer and human blood serum.