Inhibition of MRP1 transport activity by phenolic and terpenic compounds isolated from Euphorbia species.
BACKGROUND
A search for inhibitors of multidrug resistance (MDR)-associated protein 1 (MRP1) was performed among the compounds isolated from Euphorbia species, plants traditionally used in folk medicine.


METHODS
Fifteen compounds with terpenic or phenolic structures (macrocyclic and polycyclic diterpenes, coumarins, stilbenes and flavonoids) were isolated from the methanol extracts of Euphorbia lagascae and Euphorbia tuckeyana or obtained by derivatization. A functional test based on measuring the efflux of fluorescent MRP1 substrate (BCECF) from human erythrocytes was employed.


RESULTS
Effective MRP1 inhibitors were identified among the stilbenes (piceatannol and its derivatives) and the flavonoids (aromadendrin, naringenin and its derivatives).


CONCLUSIONS
Euphorbia species constitute a promising source of multidrug resistance modulators.
Wesolowska
Olga
O
Department of Biophysics, Wroclaw Medical University, ul. Chalubinskiego 10, 50-368 Wroclaw, Poland. olawes@biofiz.am.wroc.pl
Wisniewski
Jerzy
J
Duarte
Noélia
N
Ferreira
Maria-José U
MJ
Michalak
Krystyna
K
D000107:Acetylation; D001692:Biological Transport / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D008745:Methylation; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D004224:Diterpenes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010636:Phenols; D010936:Plant Extracts; C421109:multidrug resistance-associated protein 1