Potent and selective inhibition of human immunodeficiency virus type 1 (HIV-1) by 5-ethyl-6-phenylthiouracil derivatives through their interaction with the HIV-1 reverse transcriptase.

• M Baba

  Department of Bacteriology, Fukushima Medical College, Japan.

• E De Clercq

  Department of Bacteriology, Fukushima Medical College, Japan.

• H Tanaka

  Department of Bacteriology, Fukushima Medical College, Japan.

• M Ubasawa

  Department of Bacteriology, Fukushima Medical College, Japan.

• H Takashima

  Department of Bacteriology, Fukushima Medical College, Japan.

• K Sekiya

  Department of Bacteriology, Fukushima Medical College, Japan.

• I Nitta

  Department of Bacteriology, Fukushima Medical College, Japan.

• K Umezu

  Department of Bacteriology, Fukushima Medical College, Japan.

• H Nakashima

  Department of Bacteriology, Fukushima Medical College, Japan.

• S Mori

  Department of Bacteriology, Fukushima Medical College, Japan.

抄録

In the search for 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine (HEPT) derivatives, we have found several 5-ethyl-6-(phenylthio)uracil analogues to be highly potent and selective inhibitors of human immunodeficiency virus (HIV) type 1. 1-Benzyloxymethyl-5-ethyl-6-phenylthiouracil, the most potent congener of the series, inhibits HIV-1 replication in a variety of cell systems, including peripheral blood lymphocytes, at a concentration of 1.5-7.0 nM, which is lower by a factor of 10(3) than the 50% antivirally effective concentration of the parent compound HEPT. The 5-ethyl-6-(phenylthio)uracil analogues, like HEPT itself, do not inhibit HIV-2 replication but do inhibit replication of 3'-azido-3'-deoxythymidine-resistant mutants of HIV-1. 1-Benzyloxy-methyl-5-ethyl-6-phenylthiouracil and its congeners are targeted at the HIV-1 reverse transcriptase (RT). They do not inhibit HIV-2 RT. They do not need to be metabolized to exert their inhibitory effect on HIV-1 RT. Yet this inhibitory effect is competitive with the natural substrate dTTP. The HEPT derivatives represent a group of RT inhibitors with a unique mode of interaction with HIV-1 RT.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 88 (6), 2356-2360, 1991-03-15

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1363107369413928320
• NII論文ID: 30016291056
• DOI: 10.1073/pnas.88.6.2356
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.88.6.2356
• データソース種別:
  • Crossref
  • CiNii Articles