RESUMO
Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives of AZT and d4T were synthesized and evaluated as anti-HIV agents. The efficacy of some of the synthesized compounds in cell cultures infected with HIV-1 was higher than that of the parent nucleosides and only slightly correlated to their stability in the phosphate buffer and human blood serum. The synthesized phosphonates are most probably prodrug forms of the corresponding nucleosides.
Assuntos
Fármacos Anti-HIV/síntese química , Foscarnet/análogos & derivados , Ácido Fosfonoacéticos/análogos & derivados , Pró-Fármacos/síntese química , Estavudina/análogos & derivados , Zidovudina/análogos & derivados , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Estabilidade de Medicamentos , Foscarnet/síntese química , Foscarnet/farmacologia , HIV-1/efeitos dos fármacos , Humanos , Hidrólise , Ácido Fosfonoacéticos/síntese química , Ácido Fosfonoacéticos/farmacologia , Pró-Fármacos/farmacologia , Estavudina/síntese química , Estavudina/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Zidovudina/síntese química , Zidovudina/farmacologiaRESUMO
New phosphorodiamides of modified nucleoside monophosphates were synthesized and their antiviral properties were evaluated.
Assuntos
Antivirais/farmacologia , Nucleotídeos/farmacologia , Compostos de Fósforo/farmacologia , Pró-Fármacos/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antivirais/química , HIV-1/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Nucleotídeos/química , Compostos de Fósforo/química , Fosforilação , Pró-Fármacos/química , Estavudina/química , Estavudina/farmacologia , Relação Estrutura-Atividade , Zidovudina/química , Zidovudina/farmacologiaRESUMO
Carbocyclic alpha, gamma-bis(nucleoside)-5,5'-triphosphonates and alpha, delta-bis(nucleoside)-5,5'-tetraphosphonates (Ap4A and Gp4G) analogues were shown to be a new type of terminating substrate of HIV reverse transcriptase. They effectively inhibited the DNA synthesis catalyzed by this enzyme in model cell-free systems, but their antiviral activity both in Rat1 fibroblast cell culture bearing MLV reverse transcriptase and in HIV-infected MT-4 cells was low. When a liposome delivery system was used, the antiviral efficacy of the compounds under study was increased.