Document Report Card

ID: ALA2010704

Journal: J Med Chem

Title: Substituted chromones as highly potent nontoxic inhibitors, specific for the breast cancer resistance protein.

Authors: Valdameri G, Genoux-Bastide E, Peres B, Gauthier C, Guitton J, Terreux R, Winnischofer SM, Rocha ME, Boumendjel A, Di Pietro A.

Abstract: A series of 13 disubstituted chromones was synthesized. Two types of substituents, on each side of the scaffold, contributed to both the potency of ABCG2 inhibition and the cytotoxicity. The best compound, 5-(4-bromobenzyloxy)-2-(2-(5-methoxyindolyl)ethyl-1-carbonyl)-4H-chromen-4-one (6g), displayed high-affinity inhibition and low cytotoxicity, giving a markedly high therapeutic index. The chromone derivative specifically inhibited ABCG2 versus other multidrug ABC transporters and was not transported. It constitutes a highly promising candidate for in vivo chemosensitization of ABCG2-expressing tumors.

CiteXplore: 22165858

DOI: 10.1021/jm201404w