title: Flavonoids from eight tropical plant species that inhibit the multidrug resistance transporter ABCG2.
abstract: Overexpression of ABCG2, a membrane-bound multi-drug transporter, can make tumor cells resistant to treatment with conventional chemotherapeutic agents. A high-throughput screening effort with the NCI repository of natural product extracts revealed that eight tropical plant extracts significantly inhibited the function of ABCG2. This activity was tracked throughout the extract fractionation process to a series of ABCG2 inhibitory flavonoids (1-13). Their structures were identified by a combination of NMR, mass spectrometry, and circular dichroism studies, and this resulted in the elucidation of (2S)-5,7,3'-trihydroxy-4'-methoxy-8-(3''-methylbut-2''-enyl)-flavonone (1), (2S)-5,7,3',5'-tetrahydroxy-8-[3'',8''-dimethylocta-2''(E),7''-dienyl]flavonone (3), and 5,7,3'-trihydroxy-3,5'-dimethoxy-2'-(3'-methylbut-2-enyl)flavone (12) as new compounds.
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, NCI-Frederick, Frederick, Maryland 21702, United States.
authors.forename: Muhammad Ali
authors.initials: MA
authors.lastname: Versiani
authors.forename: Thushara
authors.initials: T
authors.lastname: Diyabalanage
authors.forename: Ranjala
authors.initials: R
authors.lastname: Ratnayake
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Henrich
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
authors.forename: James B
authors.initials: JB
authors.lastname: McMahon
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Gustafson
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D054547:National Cancer Institute (U.S.); D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D014481:United States
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D005419:Flavonoids; D009363:Neoplasm Proteins