Synthesis, in vitro anti-HIV and anti-hepatitis B activities and pharmacokinetic properties of amphiphilic heterodinucleoside phosphates containing ddC and AZT.
Amphiphilic heterodinucleoside phosphates containing AZT and ddC as antiviral monomer were synthesized according to the hydrogenphosphonate method and evaluated in vitro against HIV. dT-N4-pamddC was the most active (IC50 = 40 microM, EC50 = 80 nM) and least toxic (TI = 524) dimer and it exhibited also strong antiviral effects against eight AZT-resistant HIV strains. The ddC-containing heterodimers additionally inhibited HBV replication by 50-80% at 50 microM in Hep G2 2.2.15 cells.
Schwendener
R A
RA
Dept. of Pathology, University Hospital, Zürich, Germany.
Peghini
P A
PA
Ludwing
P S
PS
Schott
H
H
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D015215:Zidovudine; D016047:Zalcitabine