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: Wim Pluymers, Godwin Pais, Bénédicte Van Maele, Christophe Pannecouque, Valery Fikkert, Terrence R Burke Jr, Erik De Clercq, Myriam Witvrouw, Nouri Neamati, Zeger Debyser
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 46 Issue 10 Pg. 3292-7 (Oct 2002) ISSN: 0066-4804 [Print] United States
• PMID: 12234864 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetoacetates
• HIV Integrase Inhibitors
• L 708906
• HIV Integrase

Topics

• Acetoacetates (chemistry, pharmacology)
• Animals
• Cells, Cultured
• HIV Integrase (drug effects)
• HIV Integrase Inhibitors (chemistry, pharmacology)
• HIV-1 (drug effects, enzymology)
• HIV-2 (drug effects)
• Humans
• Microbial Sensitivity Tests
• Simian Immunodeficiency Virus (drug effects)
• Structure-Activity Relationship
• Virus Integration (drug effects)
• Virus Replication (drug effects)