Quinoxaline-substituted chalcones as new inhibitors of breast cancer resistance protein ABCG2: polyspecificity at B-ring position

• DOI: 10.2147/dddt.s56625
• Publication Date: 2014-05-28T01:16:27Z
• Authors: Attilio Di Pietro; Louise D. Chiarad...; Charlotte Gauthier; Alessandra Mascar...; Rosendo A. Yunes; Ricardo J. Nunes; Tania B. Crecynsk...; Paulo C. Leal; Evelyn Winter; Gustavo Gozzi; Nathalia Daflon-Y...; Raphael Terreux; Silvia Cadena
• Keywords: Quinoxaline; Abcg2; Mitoxantrone; Chalcone

Abstract: A series of chalcones substituted by a quinoxaline unit at the B-ring were synthesized and tested as inhibitors breast cancer resistance protein-mediated mitoxantrone efflux. These compounds appeared more efficient than analogs containing other substituents such 2-naphthyl or 3,4-methylenedioxyphenyl while an intermediate inhibitory activity was obtained with 1-naphthyl group. In all cases, two three methoxy groups had to be present on phenyl A-ring produce maximal inhibition. Molecular modeling indicated both electrostatic steric positive contributions. higher potency observed when group shifted B-ring, indicating preferences among polyspecificity Keywords: ABC transporters, protein (BCRP)/ABCG2, derivatives, structure–activity relationships, drug efflux