Substituted Chromones as Highly Potent Nontoxic Inhibitors, Specific for the Breast Cancer Resistance Protein
Journal of Medicinal Chemistry2011Vol. 55(2), pp. 966–970
Citations Over TimeTop 10% of 2011 papers
Gláucio Valdameri, Estelle Genoux‐Bastide, Basile Pérès, Charlotte Gauthier, Jérôme Guitton, Raphaël Terreux, Sheila Maria Brochado Winnischofer, Maria Eliane Merlin Rocha, Ahcène Boumendjel, Attilio Di Pietro
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.
Related Papers
- → ABC Transporter-Mediated Multidrug-Resistant Cancer(2019)232 cited
- Multidrug resistance and pharmacological protection mediated by the breast cancer resistance protein (BCRP/ABCG2).(2002)
- → Effect of the breast-cancer resistance protein on atypical multidrug resistance(2000)79 cited
- → 9-Deazapurines as Broad-Spectrum Inhibitors of the ABC Transport Proteins P-Glycoprotein, Multidrug Resistance-Associated Protein 1, and Breast Cancer Resistance Protein(2017)64 cited
- → Human ABC Transporter ABCG2 in Cancer Chemotherapy: Drug Molecular Design to Circumvent Multidrug Resistance(2012)9 cited