Evelyn Winter 1 , 2 , Gustavo Jabor Gozzi 1 , 3 , Louise Domeneghini Chiaradia-Delatorre 4 , Nathalia Daflon-Yunes 1 , Raphael Terreux 5 , Charlotte Gauthier 1 , Alessandra Mascarello 4 , Paulo César Leal 4 , Silvia M Cadena 3 , Rosendo Augusto Yunes 4 , Ricardo José Nunes 4 , Tania Beatriz Creczynski-Pasa 2 , Attilio Di Pietro 1
27 May 2014
A series of chalcones substituted by a quinoxaline unit at the B-ring were synthesized and tested as inhibitors of breast cancer resistance protein-mediated mitoxantrone efflux. These compounds appeared more efficient than analogs containing other B-ring substituents such as 2-naphthyl or 3,4-methylenedioxyphenyl while an intermediate inhibitory activity was obtained with a 1-naphthyl group. In all cases, two or three methoxy groups had to be present on the phenyl A-ring to produce a maximal inhibition. Molecular modeling indicated both electrostatic and steric positive contributions. A higher potency was observed when the 2-naphthyl or 3,4-methylenedioxyphenyl group was shifted to the A-ring and methoxy substituents were shifted to the phenyl B-ring, indicating preferences among polyspecificity of inhibition.