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Synergistic inhibition of human immunodeficiency virus type 1 replication by 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU) and azidothymidine in vitro.

Abstract
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.
AuthorsM Baba, M Ito, S Shigeta, H Tanaka, T Miyasaka, M Ubasawa, K Umezu, R T Walker, E De Clercq
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 35 Issue 7 Pg. 1430-3 (Jul 1991) ISSN: 0066-4804 [Print] United States
PMID1929304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil
  • Zidovudine
  • Uracil
Topics
  • Antiviral Agents (pharmacology)
  • Cells, Cultured
  • Cytopathogenic Effect, Viral (drug effects)
  • Drug Synergism
  • HIV-1 (drug effects, physiology)
  • Humans
  • Uracil (analogs & derivatives, pharmacology)
  • Virus Replication (drug effects)
  • Zidovudine (pharmacology)

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