Abstract

Nonplanar 9,10-dihydroacridines were synthesized as promising C₂ symmetric molecular scaffolds as inhibitors of the transmembrane efflux pump ABCB1. Within the series structure-activity relationships are discussed revealing the importance of hydrogen bond acceptor functions. A selectivity of ABCB1 inhibition is demonstrated for selected candidates and a bioanalytical study proved nontoxicity as well as missing ABCB1 substrate properties. The results encourage to further develop the promising class of ABCB1 inhibitors.

Keywords: ABCB1 inhibitor, ABCB1 substrate properties, structure-activity relationships.

Graphical Abstract