Inhibition of human immunodeficiency virus type 1 integration by diketo derivatives

Antimicrob Agents Chemother. 2002 Oct;46(10):3292-7. doi: 10.1128/AAC.46.10.3292-3297.2002.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetoacetates / chemistry
  • Acetoacetates / pharmacology*
  • Animals
  • Cells, Cultured
  • HIV Integrase / drug effects*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / 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


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