Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2

Ahcene Boumendjel; Sira Macalou; Abdelhakim Ahmed-Belkacem; Madeleine Blanc; Attilio Di Pietro

doi:10.1016/j.bmc.2007.02.017

Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2

Ahcene Boumendjel, Sira Macalou, Abdelhakim Ahmed-Belkacem, Madeleine Blanc, Attilio Di Pietro

Experimental Radiation Oncology

Research output: Contribution to journal › Article › peer-review

94 Scopus citations

Abstract

The breast cancer resistance protein (BCRP, ABCG2) is among the latest discovered ABC proteins to be involved in MDR phenotype and for which only few inhibitors are known. In continuing our program aimed at discovering efficient multidrug resistance modulators, we conceived and synthesized new acridones as ABCG2 inhibitors. The design of target molecules was based on earlier results dealing with ABCG2 inhibition with flavone and chromone derivatives. The human wild-type (R482) ABCG2-transfected cells were used for rational screening of inhibitory acridones. The synthesis of target compounds, the inhibitory activity against ABCG2, and structure-activity relationships are described. One of the acridones was even more potent than the reference inhibitor, GF120918, as shown by its ability to inhibit mitoxantrone efflux.

Original language	English (US)
Pages (from-to)	2892-2897
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	15
Issue number	8
DOIs	https://doi.org/10.1016/j.bmc.2007.02.017
State	Published - Apr 15 2007

Keywords

ABCG2
Acridones
BCRP
MDR

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2007.02.017

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title = "Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2",

abstract = "The breast cancer resistance protein (BCRP, ABCG2) is among the latest discovered ABC proteins to be involved in MDR phenotype and for which only few inhibitors are known. In continuing our program aimed at discovering efficient multidrug resistance modulators, we conceived and synthesized new acridones as ABCG2 inhibitors. The design of target molecules was based on earlier results dealing with ABCG2 inhibition with flavone and chromone derivatives. The human wild-type (R482) ABCG2-transfected cells were used for rational screening of inhibitory acridones. The synthesis of target compounds, the inhibitory activity against ABCG2, and structure-activity relationships are described. One of the acridones was even more potent than the reference inhibitor, GF120918, as shown by its ability to inhibit mitoxantrone efflux.",

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author = "Ahcene Boumendjel and Sira Macalou and Abdelhakim Ahmed-Belkacem and Madeleine Blanc and {Di Pietro}, Attilio",

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AU - Blanc, Madeleine

AU - Di Pietro, Attilio

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Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2

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