RESUMEN
3'-Azido-3'-deoxythymidine-5'-phosphate diglyceride (16:0/18:1 omega 9), a phosphatic acid conjugate of AZT, is active against HIV replication in H9 cells and syncytia formation in MOLT-3 cells. The activities rank as AZT greater than pure conjugate greater than conjugate in mixed liposomes, with the pure conjugate having about one-third the activity of free AZT. The compound binds very rapidly to serum lipoproteins, but not to serum albumin, alpha and beta globulins, or red cells. Pancreatic phospholipase A2 hydrolyzes it to the lysophosphatidic acid conjugate.
Asunto(s)
Antivirales , Diglicéridos , Glicéridos , VIH/efectos de los fármacos , Zidovudina/administración & dosificación , Proteínas Sanguíneas/metabolismo , Células Cultivadas , Fenómenos Químicos , Química Física , Relación Dosis-Respuesta a Droga , VIH/crecimiento & desarrollo , Humanos , Técnicas In Vitro , Liposomas , Proteínas de los Retroviridae/metabolismo , Replicación Viral/efectos de los fármacosRESUMEN
Disodium palmityl phosphonoformate, a novel lipid phosphoester of the anti HIV agent phosphonoformate (foscarnet), inhibits HIV replication in H9 cells and syncytia formation in MOLT-3 cells as effectively as foscarnet itself, as shown by dose-response data from assays for expression of p17 and p24 viral antigens and syncytia formation. Protein binding studies indicate that in serum, the derivative exists bound to albumin and the lipoproteins, and would therefore be likely to exhibit improved serum lifetime in vivo.