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Inhibition of human immunodeficiency virus type 1 integration by diketo derivatives

  1. Author:
    Pluymers, W.
    Pais, G.
    Van Maele, B.
    Pannecouque, C.
    Fikkert, V.
    Burke, T. R.
    De Clercq, E.
    Witvrouw, M.
    Neamati, N.
    Debyser, Z.

  2. Author Address

    Catholic Univ Louvain, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louvain, Belgium Catholic Univ Louvain, Rega Inst Med Res, B-3000 Louvain, Belgium NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA Univ So Calif, Sch Pharm, Los Angeles, CA 90089 USA Debyser Z Catholic Univ Louvain, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louvain, Belgium
    1. Year: 2002
  2. Journal: Antimicrobial Agents and Chemotherapy
    1. 46
    2. 10
    3. Pages: 3292-3297
  4. Type of Article: Article
  1. Abstract:

    A series of diketo derivatives was found to inhibit human immunodeficiency virus type 1 (HIV-1) integrase activity. Only L-708,906 inhibited the replication of HIV-1(IIIB) (50% effective concentration, 12 muM), HIV-1 clinical strains, HIV-1 strains resistant to reverse transcriptase or fusion inhibitors, HIV-2 (ROD strain) and simian immunodeficiency virus (MAC(251)). The combinations of L-708,906 with zidovudine, nevirapine, or nelfinavir proved to be subsynergistic. In cell culture, addition of L-708,906 could be postponed for 7 It after infection, a moment coinciding with HIV integration. Inhibition of integration in cell culture was confirmed by quantitative Alu-PCR.

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