Metabolic O-demethylation does not alter the influence of isoflavones on the biophysical properties of membranes and MRP1-like protein transport activity

Arch Biochem Biophys. 2005 Jan 15;433(2):428-34. doi: 10.1016/j.abb.2004.10.004.

Abstract

Multidrug resistance transporter MRP1 could be effectively inhibited by some flavonoids. The influence of the two pairs of isoflavones: formononetin/daidzein and biochanin A/genistein on the efflux of fluorescent substrate of MRP1-like protein from erythrocytes and biophysical properties of lipid membranes has been compared. Compounds in each pair differ by the substituent in position 4' of B ring of isoflavone molecule. In the process of O-demethylation, CH(3) group (present in formonetin and biochanin A) is replaced by hydrogen (daidzein, genistein). Inhibition of MRP1-like protein transport activity by methylated and demethylated isoflavones was very similar. Their influence on lipid thermotropic properties and fluidity of lipid bilayer was not also significantly different.

Publication types

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

MeSH terms

  • 1,2-Dipalmitoylphosphatidylcholine / metabolism*
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / metabolism*
  • Biophysical Phenomena
  • Biophysics*
  • Dihydropyridines / chemistry
  • Erythrocytes / metabolism*
  • Female
  • Genes, MDR
  • Genistein / chemistry
  • Genistein / metabolism
  • Humans
  • Indomethacin / metabolism
  • Isoflavones / chemistry
  • Isoflavones / metabolism*
  • Male
  • Methylation
  • Middle Aged
  • Molecular Structure
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Octanols / chemistry
  • Plant Preparations / chemistry
  • Plant Preparations / metabolism
  • Reference Standards
  • Temperature
  • Thermodynamics
  • Water / chemistry

Substances

  • 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester
  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Dihydropyridines
  • Isoflavones
  • Multidrug Resistance-Associated Proteins
  • Octanols
  • Plant Preparations
  • Water
  • 1,2-Dipalmitoylphosphatidylcholine
  • formononetin
  • daidzein
  • Genistein
  • biochanin A
  • Indomethacin
  • multidrug resistance-associated protein 1