Denbinobin, a naturally occurring 1,4-phenanthrenequinone, inhibits HIV-1 replication through an NF-kappaB-dependent pathway

Biochem Pharmacol. 2008 Nov 15;76(10):1240-50. doi: 10.1016/j.bcp.2008.09.006. Epub 2008 Sep 18.

Abstract

Anthraquinones and structurally related compounds have been recently shown to exert antiviral activities and thus exhibit a therapeutic potential. In this study we report the isolation of the 1,4-phenanthrenequinone, denbinobin, from a variety of Cannabis sativa. Denbinobin does not affect the reverse transcription and integration steps of the viral cycle but prevents HIV-1 reactivation in Jurkat T cells activated by TNFalpha, mAbs anti-CD3/CD28 or PMA. In addition, denbinobin inhibits HIV-1-LTR activity at the level of transcription elongation and also TNFalpha-induced HIV-1-LTR transcriptional activity. We found that denbinobin prevents the binding of NF-kappaB to DNA and the phosphorylation and degradation of NF-kappaB inhibitory protein, IkappaBalpha, and inhibits the phosphorylation of the NF-kappaB p65 subunit in TNFalpha-stimulated cells. These results highlight the potential of the NF-kappaB transcription factor as a target for natural anti-HIV-1 compounds such as 1,4-phenanthrenequinones, which could serve as lead compounds for the development of an alternative therapeutic approach against AIDS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / chemistry
  • Anthraquinones / isolation & purification
  • Anthraquinones / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Jurkat Cells
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Phenanthrenes / chemistry
  • Phenanthrenes / isolation & purification
  • Phenanthrenes / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Virus Replication / drug effects*
  • Virus Replication / physiology

Substances

  • Anthraquinones
  • NF-kappa B
  • Phenanthrenes
  • Plant Extracts
  • denbinobin
  • 1,4-phenanthrenequinone