title: Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance.
abstract: The inhibition of ABC (ATP binding cassette) transporters is considered a powerful tool to reverse multidrug resistance. Zosuquidar featuring a difluorocyclopropyl-annulated dibenzosuberyl moiety has been found to be an inhibitor of the P-glycoprotein, one of the best-studied multidrug efflux pumps. Twelve 5-oxyisoquinoline derivatives, which are analogues of zosuquidar wherein the dibenzosuberyl-piperazine moiety is replaced by either a diarylaminopiperidine or a piperidone-derived acetal or thioacetal group, have been synthesized as pure enantiomers. Their inhibitory power has been evaluated for the bacterial multidrug-resistance ABC transporter LmrCD and fungal Pdr5. Four of the newly synthesized compounds reduced the transport activity to a higher degree than zosuquidar, being up to fourfold more efficient than the lead compound in the case of LmrCD and about two times better for Pdr5.
authors.affiliation: Institute of Organic and Macromolecular Chemistry, University of Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Dittrich
authors.forename: Nils
authors.initials: N
authors.lastname: Hanekop
authors.forename: Nacera
authors.initials: N
authors.lastname: Infed
authors.forename: Lutz
authors.initials: L
authors.lastname: Schmitt
authors.forename: Manfred
authors.initials: M
authors.lastname: Braun