Influence of the skeleton on the cytotoxicity of flavonoids

Bioorg Med Chem. 2012 Feb 1;20(3):1231-9. doi: 10.1016/j.bmc.2011.12.038. Epub 2011 Dec 30.

Abstract

Analogs of 3'-amino-5-hydroxy-3,6,7,8,4'-pentamethoxy-flavone, a strongly cytotoxic and antimitotic semisynthetic flavone, were synthesized in the aurone, isoflavone and isoflavanone series. Comparison of the biological activity of these new compounds with the reference showed a potent cytotoxicity only in the flavone series. Influence of the hydroxy group (at C-5 in flavones, at C-4 in aurones) on the cytotoxicity, known to be favorable in flavones, was found to be detrimental in aurones. This observation was related to the hydrogen bonding formed with the carbonyl group, strong in the flavones, but of weak intensity in the aurones.

MeSH terms

  • Benzofurans / chemistry
  • Benzofurans / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Chalcones / chemistry
  • Chalcones / pharmacology
  • Flavonoids / chemistry*
  • Flavonoids / pharmacology*
  • Humans
  • Isoflavones / chemistry
  • Isoflavones / pharmacology
  • Structure-Activity Relationship
  • Tubulin / metabolism
  • Tubulin Modulators / chemistry*
  • Tubulin Modulators / pharmacology*

Substances

  • Benzofurans
  • Chalcones
  • Flavonoids
  • Isoflavones
  • Tubulin
  • Tubulin Modulators
  • aurone