Metabolic O-demethylation does not alter the influence of isoflavones on the biophysical properties of membranes and MRP1-like protein transport activity.
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.
Łania-Pietrzak
Barbara
B
Department of Biophysics, Wrocław Medical University, Poland.
Hendrich
Andrzej B
AB
Zugaj
Jarosław
J
Michalak
Krystyna
K
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism*; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000378:metabolism*; D055592:Biophysical Phenomena; D001703:Biophysics; D004095:Dihydropyridines / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D019450:Genes, MDR; D019833:Genistein / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000378:metabolism; D007529:Isoflavones / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D000442:Octanols / Q000737:chemistry; D028321:Plant Preparations / Q000737:chemistry / Q000378:metabolism; D012015:Reference Standards; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D015060:1,2-Dipalmitoylphosphatidylcholine; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D004095:Dihydropyridines; D019833:Genistein; D007213:Indomethacin; D007529:Isoflavones; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000442:Octanols; D028321:Plant Preparations; D014867:Water; C466879:2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester; C007768:formononetin; C004742:daidzein; C004541:biochanin A; C421109:multidrug resistance-associated protein 1