Lipid conjugates of antiretroviral agents. I. Azidothymidine-monophosphate-diglyceride: Anti-HIV activity, physical properties, and interaction with plasma proteins

3′-Azido-3′-deoxythymidine-5′-phosphate diglyceride ( 16:0 18:1 ω9 ), 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 > pure conjugate > 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, α and β globulins, or red cells. Pancreatic phospholipase A 2 hydrolyzes it to the lysophosphatidic acid conjugate.