Chromone and chromanone derivatives as strand transfer inhibitors of HIV-1 integrase

Arch Pharm Res. 2008 Jan;31(1):1-5. doi: 10.1007/s12272-008-1111-z.

Abstract

HIV-1 integrase catalyzes terminal cleavage at the 3' end of the proviral DNA, removing a pair of bases and causing strand transfer by joining the 3' end to 5'-phosphates in the target DNA. Several aryl 1,3-diketo acids that can inhibit the strand transfer reaction of HIV-1 IN have been identified. Here we synthesized a new series of compounds with a chromone or chromanone ring as conformationally constrained scaffolds of 1,3-diketo acids, and then tested their ability to inhibit HIV-1 IN-mediated strand transfer. All compounds moderately inhibited HIV-1 IN activity, indicating that the conformational restriction of one keto group into a chromone or chromanone ring decreases inhibition of the HIV-1 IN strand transfer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / chemical synthesis
  • Anthraquinones / chemistry
  • Anthraquinones / pharmacology*
  • Chromones / chemical synthesis
  • Chromones / chemistry
  • Chromones / pharmacology*
  • DNA, Viral / drug effects
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Hydrogen Bonding
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation

Substances

  • Anthraquinones
  • Chromones
  • DNA, Viral
  • HIV Integrase Inhibitors
  • Indicators and Reagents
  • chaetomanone