title: Discovery of substituted 1,4-dihydroquinolines as novel promising class of P-glycoprotein inhibitors: First structure-activity relationships and bioanalytical studies.
abstract: Multidrug resistance (mdr) is the most important problem in the therapeutical treatment of cancer. One central problem in the resistance proceeding is the expression of transmembrane efflux pumps which transport drugs out of the cells. We developed novel substituted 1,4-dihydroquinolines as inhibitors of the transmembrane efflux pump P-glycoprotein. Structure-activity relationships are discussed for this first series. Promising active inhibitors have been identified and first bioanalytical studies have been carried out to address questions of cellular toxicity, P-gp substrate as well as mdr reversal properties.
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Hemmer
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Krawczyk
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Simon
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany. Electronic address: andreas.hilgeroth@pharmazie.uni-halle.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hilgeroth
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C544515:1,4-dihydroquinoline; D018435:ATP Binding Cassette Transporter, Subfamily B; D011804:Quinolines
keywords: 1,4-Dihydroquinolines; Mdr reversal; P-gp inhibitor; Structure–activity relationships; Substrate properties