title: Development of small-molecule P-gp inhibitors of the N-benzyl 1,4-dihydropyridine type: novel aspects in SAR and bioanalytical evaluation of multidrug resistance (MDR) reversal properties.
abstract: Novel series of N-benzyl 1,4-dihydropyridines have been prepared by facile syntheses. All relevant substituents of the molecular scaffold have been varied. The resulting compounds were biologically evaluated as P-glycoprotein (P-gp) inhibitors. Substitutions of the N-benzyl residue favour biological activity beside respective 3-ester functions. Most active compounds were further evaluated as multidrug resistance (MDR) modulators to restore the cytotoxic properties of varying daunorubicin applications.
authors.affiliation: Institute of Pharmacy, Martin Luther University, 06120 Halle, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Baumert
authors.forename: Marianne
authors.initials: M
authors.lastname: Günthel
authors.forename: Sören
authors.initials: S
authors.lastname: Krawczyk
authors.forename: Marc
authors.initials: M
authors.lastname: Hemmer
authors.forename: Tom
authors.initials: T
authors.lastname: Wersig
authors.forename: Andreas
authors.initials: A
authors.lastname: Langner
authors.forename: Joséf
authors.initials: J
authors.lastname: Molnár
authors.forename: Hermann
authors.initials: H
authors.lastname: Lage
authors.forename: Andreas
authors.initials: A
authors.lastname: Hilgeroth
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D003630:Daunorubicin