A biflavonoid from Luxemburgia nobilis as inhibitor of DNA topoisomerases

Planta Med. 2005 Jun;71(6):561-3. doi: 10.1055/s-2005-864159.

Abstract

The biflavonoid 2'',3''-diidroochnaflavone ( 1), isolated from the leaves of Luxemburgia nobilis, was cytotoxic to murine Ehrlich carcinoma (IC50 = 17.2 microM) and human leukemia K562 cells (IC50 = 89.0 microM) in a concentration-dependent manner in 45 h cell culture. The acetyl (1a) and methyl (1b) derivatives of 1 were not cytotoxic to these tumour cells at 67.0 and 82.0 microM concentrations, respectively. Biflavonoid 1 as well 1a inhibit the activity of human DNA topoisomerases I and II-alpha as observed in relaxation and decatenation assays. In addition, we show that 1 is a DNA interacting agent, which causes DNA unwinding in an assay with topoisomerase I. Also, spectrophotometric titration of 1 with DNA resulted in a pronounced hypochromic effect.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Biflavonoids / administration & dosage
  • Biflavonoids / pharmacology
  • Biflavonoids / therapeutic use
  • Cell Line, Tumor / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Ochnaceae*
  • Phytotherapy*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Topoisomerase I Inhibitors*

Substances

  • Antineoplastic Agents, Phytogenic
  • Biflavonoids
  • Enzyme Inhibitors
  • Plant Extracts
  • Topoisomerase I Inhibitors