Inhibition of human immunodeficiency virus type 1 integration by diketo derivatives.
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.
Pluymers
Wim
W
Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, Belgium.
Pais
Godwin
G
Van Maele
Bénédicte
B
Pannecouque
Christophe
C
Fikkert
Valery
V
Burke
Terrence R
TR
De Clercq
Erik
E
Witvrouw
Myriam
M
Neamati
Nouri
N
Debyser
Zeger
Z
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
D000090:Acetoacetates; D019428:HIV Integrase Inhibitors; C403887:L 708906; D019427:HIV Integrase