Isoflavones with unusually modified B-rings and their evaluation as antiproliferative agents

Bioorg Med Chem Lett. 2009 Nov 15;19(22):6473-6. doi: 10.1016/j.bmcl.2009.08.084. Epub 2009 Aug 28.

Abstract

Six novel isoflavone derivatives along with four known isoflavones were isolated from a culture of a highly nickel-resistant strain of Streptomyces mirabilis from a former uranium mining area. The structures of 7-hydroxy-3',5'-dihydroxyisoflavone (5), 5,7-dihydroxy-3',5'-dihydroxyisoflavone (6), 2'-hydroxy-3'-methoxygenistein (7), as well as hydroisoflavones A-C (8-10) were elucidated by MS and NMR analyses. Compounds 8-10 feature yet unprecedented types of non-aromatic, hydroxylated B rings, which result from plant isoflavone biotransformation. All new compounds display weak cytotoxic but potent antiproliferative activities. The anti-oestrogenic properties of 8 against MCF-7 human breast cancer cell line (GI(50): 6 microM) is even higher than the reference compound genistein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Antioxidants / analysis
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Biotransformation
  • Caco-2 Cells / pathology
  • Carcinogens / pharmacology
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Genistein / analysis
  • Genistein / metabolism
  • Genistein / therapeutic use
  • Humans
  • Isoflavones / chemistry
  • Isoflavones / therapeutic use*
  • Models, Molecular
  • Oxidative Stress / drug effects
  • Plant Bark / chemistry

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Antioxidants
  • Carcinogens
  • Isoflavones
  • Genistein