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

Małgorzata Bobrowska-Hägerstrand, Anna Wróbel, Lucyna Mrówczyñska, Thomas Söderström, Yoshiaki Shirataki, Noboru Motohashi, J. Molnár, Krystyna Michalak, Henry Hägerstrand

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)463-469
Number of pages7
JournalOncology Research
Volume13
Issue number11
Publication statusPublished - 2002

Fingerprint

Flavanones
Structure-Activity Relationship
Flavonoids
Human Activities
Inhibitory Concentration 50
Erythrocytes
Benzbromarone
Flavones
Stilbenes
Isoflavones
Genistein
Molecular Structure
Indomethacin
Hydroxyl Radical
6-carboxyfluorescein
prenyl

Keywords

  • BCPCF
  • Benzbromarone
  • Flavanone
  • Indomethacin
  • Multidrug resistance
  • Red blood cell
  • Structure-activity analysis

ASJC Scopus subject areas

  • Cancer Research

Cite this

Bobrowska-Hägerstrand, M., Wróbel, A., Mrówczyñska, L., Söderström, T., Shirataki, Y., Motohashi, N., ... Hägerstrand, H. (2002). Flavonoids as Inhibitors of MRP1-Like Efflux Activity in Human Erythrocytes. A Structure-Activity Relationship Study. Oncology Research, 13(11), 463-469.

Flavonoids as Inhibitors of MRP1-Like Efflux Activity in Human Erythrocytes. A Structure-Activity Relationship Study. / Bobrowska-Hägerstrand, Małgorzata; Wróbel, Anna; Mrówczyñska, Lucyna; Söderström, Thomas; Shirataki, Yoshiaki; Motohashi, Noboru; Molnár, J.; Michalak, Krystyna; Hägerstrand, Henry.

In: Oncology Research, Vol. 13, No. 11, 2002, p. 463-469.

Research output: Contribution to journalArticle

Bobrowska-Hägerstrand, M, Wróbel, A, Mrówczyñska, L, Söderström, T, Shirataki, Y, Motohashi, N, Molnár, J, Michalak, K & Hägerstrand, H 2002, 'Flavonoids as Inhibitors of MRP1-Like Efflux Activity in Human Erythrocytes. A Structure-Activity Relationship Study', Oncology Research, vol. 13, no. 11, pp. 463-469.
Bobrowska-Hägerstrand M, Wróbel A, Mrówczyñska L, Söderström T, Shirataki Y, Motohashi N et al. Flavonoids as Inhibitors of MRP1-Like Efflux Activity in Human Erythrocytes. A Structure-Activity Relationship Study. Oncology Research. 2002;13(11):463-469.
Bobrowska-Hägerstrand, Małgorzata ; Wróbel, Anna ; Mrówczyñska, Lucyna ; Söderström, Thomas ; Shirataki, Yoshiaki ; Motohashi, Noboru ; Molnár, J. ; Michalak, Krystyna ; Hägerstrand, Henry. / Flavonoids as Inhibitors of MRP1-Like Efflux Activity in Human Erythrocytes. A Structure-Activity Relationship Study. In: Oncology Research. 2002 ; Vol. 13, No. 11. pp. 463-469.
@article{5485d3048e0f4c46b04a2611e83e97f4,
title = "Flavonoids as Inhibitors of MRP1-Like Efflux Activity in Human Erythrocytes. A Structure-Activity Relationship Study",
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",
author = "Małgorzata Bobrowska-H{\"a}gerstrand and Anna Wr{\'o}bel and Lucyna Mr{\'o}wczy{\~n}ska and Thomas S{\"o}derstr{\"o}m and Yoshiaki Shirataki and Noboru Motohashi and J. Moln{\'a}r and Krystyna Michalak and Henry H{\"a}gerstrand",
year = "2002",
language = "English",
volume = "13",
pages = "463--469",
journal = "Oncology Research",
issn = "0965-0407",
publisher = "Cognizant Communication Corporation",
number = "11",

}

TY - JOUR

T1 - Flavonoids as Inhibitors of MRP1-Like Efflux Activity in Human Erythrocytes. A Structure-Activity Relationship Study

AU - Bobrowska-Hägerstrand, Małgorzata

AU - Wróbel, Anna

AU - Mrówczyñska, Lucyna

AU - Söderström, Thomas

AU - Shirataki, Yoshiaki

AU - Motohashi, Noboru

AU - Molnár, J.

AU - Michalak, Krystyna

AU - Hägerstrand, Henry

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - BCPCF

KW - Benzbromarone

KW - Flavanone

KW - Indomethacin

KW - Multidrug resistance

KW - Red blood cell

KW - Structure-activity analysis

UR - http://www.scopus.com/inward/record.url?scp=0842348982&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0842348982&partnerID=8YFLogxK

M3 - Article

VL - 13

SP - 463

EP - 469

JO - Oncology Research

JF - Oncology Research

SN - 0965-0407

IS - 11

ER -