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 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.
Steim
J M
JM
Department of Chemistry, Brown University, Providence, RI 02912.
Camaioni Neto
C
C
Sarin
P S
PS
Sun
D K
DK
Sehgal
R K
RK
Turcotte
J G
JG
D000998:Antiviral Agents; D001798:Blood Proteins / Q000378:metabolism; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004075:Diglycerides; D004305:Dose-Response Relationship, Drug; D005989:Glycerides; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D012191:Retroviridae Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000008:administration & dosage*
D000998:Antiviral Agents; D001798:Blood Proteins; D004075:Diglycerides; D005989:Glycerides; D008081:Liposomes; D012191:Retroviridae Proteins; D015215:Zidovudine