title: Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines.
abstract: A library of 42 diastereoisomeric mixtures of fumitremorgin-type indolyl diketopiperazines, prepared by parallel solid-phase synthesis, was screened for Breast Cancer Resistance Protein inhibitory activity and compared with GF120918. Demethoxy-fumitremorgin C was synthesized by solid-phase techniques and tested as well. Structure-activity relationship studies have identified several potent analogues, both in assays using the T6400 mouse and the T8 human cell line, whereas low cytotoxicity was seen at effective concentrations.
authors.affiliation: Laboratory of Organic Chemistry, Institute of Molecular Chemistry, University of Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van Loevezijn
authors.forename: J D
authors.initials: JD
authors.lastname: Allen
authors.forename: A H
authors.initials: AH
authors.lastname: Schinkel
authors.forename: G J
authors.initials: GJ
authors.lastname: Koomen
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000166:Acridines / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D018432:Drug Resistance, Multiple; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008942:Mitoxantrone / Q000378:metabolism; D015394:Molecular Structure; D009363:Neoplasm Proteins; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000166:Acridines; D000970:Antineoplastic Agents; D007211:Indoles; D007546:Isoquinolines; D009363:Neoplasm Proteins; D010879:Piperazines; D044005:Tetrahydroisoquinolines; D008942:Mitoxantrone; C010522:tryptoquivaline; C083501:Elacridar