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ID: ALA1147844

Journal: Bioorg Med Chem

Title: Acridone derivatives: design, synthesis, and inhibition of breast cancer resistance protein ABCG2.

Authors: Boumendjel A, Macalou S, Ahmed-Belkacem A, Blanc M, Di Pietro A.

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.

CiteXplore: 17317193

DOI: 10.1016/j.bmc.2007.02.017