title: Inhibition of human immunodeficiency virus type 1 integration by diketo derivatives.
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(III(B)) (50% effective concentration, 12 micro M), 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 h after infection, a moment coinciding with HIV integration. Inhibition of integration in cell culture was confirmed by quantitative Alu-PCR.
authors.affiliation: Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Pluymers
authors.forename: Godwin
authors.initials: G
authors.lastname: Pais
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Van Maele
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Valery
authors.initials: V
authors.lastname: Fikkert
authors.forename: Terrence R
authors.initials: TR
authors.lastname: Burke
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
mesh_terms: D000090:Acetoacetates / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D015302:Simian Immunodeficiency Virus / Q000187:drug effects; D013329:Structure-Activity Relationship; D016662:Virus Integration / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000090:Acetoacetates; D019428:HIV Integrase Inhibitors; C403887:L 708906; D019427:HIV Integrase