RESUMO
[Formula: see text]New phosphonate homodimers of 3'-azido-3'-deoxythymidine (AZT) and a phosphonate heterodimer of ß-L-2',3'-dideoxy-3'-thiacytidine (3TC) and AZT were synthesized. The compounds demonstrated moderate anti-HIV activity. Stability of the compounds in human blood serum was studied. A correlation between anti-HIV activity and stability was defined.
Assuntos
Lamivudina/análogos & derivados , Lamivudina/síntese química , Pró-Fármacos/síntese química , Zidovudina/análogos & derivados , Zidovudina/síntese química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Estabilidade de Medicamentos , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Hidrólise , Lamivudina/farmacocinética , Lamivudina/farmacologia , Testes de Sensibilidade Microbiana , Ressonância Magnética Nuclear Biomolecular , Pró-Fármacos/farmacologia , Zidovudina/farmacocinética , Zidovudina/farmacologiaRESUMO
The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 µM. It also inhibited replication of wild-type HSV-1 (9.7 µM) as well as an acyclovir-resistant strain (25 µM). None of the synthesised compounds showed any cytotoxicity.
Assuntos
Aciclovir/análogos & derivados , Aciclovir/farmacologia , Antivirais/química , Antivirais/farmacologia , HIV-1/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Aciclovir/síntese química , Animais , Antivirais/síntese química , Chlorocebus aethiops , Células HEK293 , Infecções por HIV/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Humanos , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
New phosphorodiamides of modified nucleoside monophosphates were synthesized and their antiviral properties were evaluated.