Synergistic inhibition of human immunodeficiency virus type 1 replication by 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU) and azidothymidine in vitro.
A novel 6-substituted acyclouridine derivative, 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU), has recently proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. Combinations of 3'-azido-2',3'-dideoxythymidine (AZT) and E-EPU synergistically inhibit the replication of HIV-1 in MT-4 cells, whereas the cytotoxic effects of AZT and E-EPU on mock-infected MT-4 cells are not enhanced by the drug combination. Synergistic inhibition of HIV-1 replication has also been observed in peripheral blood lymphocytes. These results indicate that the combination of AZT and E-EPU should be further pursued in the treatment of AIDS.
Department of Bacteriology, Fukushima Medical College, Japan.
M
M
Baba
M
M
Ito
S
S
Shigeta
H
H
Tanaka
T
T
Miyasaka
M
M
Ubasawa
K
K
Umezu
R T
RT
Walker
E
E
De Clercq
D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; C071166:5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil; D015215:Zidovudine; D014498:Uracil