Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines.
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.
van Loevezijn
A
A
Laboratory of Organic Chemistry, Institute of Molecular Chemistry, University of Amsterdam, The Netherlands.
Allen
J D
JD
Schinkel
A H
AH
Koomen
G J
GJ
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
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