Flavonoids as Inhibitors of MRP1-Like Efflux Activity in Human Erythrocytes. A Structure–Activity Relationship Study

$79.00 plus tax (Refund Policy)

Buy Article:

Abstract:

The potency of flavonoids (isoflavones, flavones, and flavanones) to inhibit efflux of 2′,7′-bis-(carboxypropyl)-5(6)-carboxyfluorescein (BCPCF) from human erythrocytes was investigated. Structure–activity relationship analysis showed that the strongest inhibitors were found among flavanones bearing a hydrophobic prenyl, geranyl, or lavandulyl group at position 8 (and hydroxyl groups at 5 and 7) in ring A. A prenyl group at position 5′ or stilbene at positions 4′–5′ in ring B further seemed to increase inhibitor potency. The most efficient flavanones, euchrestaflavanone A and sophoraflavanone H, were ∼20 times more efficient than genistein, and induced 50% inhibition of BCPCF efflux (IC50) at 3 μM (60 min, 37°C). This is comparable to IC50 of benzbromarone (4 μM) and lower than IC50 of indomethacin (10 μM), both known MRP1 (ABCC1) inhibitors. It is suggested that BCPCF efflux is mainly due to MRP1 activity. Our results indicate that flavonoid molecular structure provides a promising base for development of potent MRP1 inhibitors.

Keywords: BCPCF; Benzbromarone; Flavanone; Indomethacin; Multidrug resistance; Red blood cell; Structure–activity analysis

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000003108747983

Affiliations: 1: *Department of Biology, Åbo Akademi University, FIN-20520 Åbo/Turku, Finland 2: †Institute of Physics, Wrocław University of Technology, PL-50370 Wrocław, Poland 3: ‡Department of Cytology and Histology, A. Mickiewicz University, PL-61701, Poznan´, Poland 4: ¶Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, 350-0295 Japan 5: #Meiji Pharmaceutical University, Tokyo, 204-8588, Japan 6: **Department of Microbiology, Albert Szent-Györgyi Medical University, H-6720 Szeged, Hungary 7: ††Department of Biophysics, Wrocław Medical University, Poland

Publication date: January 1, 2003

More about this publication?
  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more