title: 4-Hydroxy-6-methoxyaurones with high-affinity binding to cytosolic domain of P-glycoprotein.
abstract: A series of 4-hydroxy-6-methoxyaurones and 4,6-dimethoxyaurones has been synthesised and tested for their binding affinity toward the nucleotide-binding domain of P-glycoprotein, an ABC (ATP-Binding Cassette) transporter which mediates the resistance of cancer cells to chemotherapy. These compounds differ from each other by the nature of the substituent on the aurone B-ring. The binding affinity seems to be linked to the nature of the substituent, as well as to the presence or the absence of a hydroxy group at position 4. The most active compounds were 4'-bromo-4-hydroxy-6-methoxyaurone and 4-hydroxy-4'-iodo-6-methoxyaurone.
authors.affiliation: Laboratory of Pharmacognosy, UMR-CNRS 5063, Grenoble Pharmacy School, La Tronche, France. Ahcene.Boumendjel@ujf-grenoble.fr
authors.forename: Ahcène
authors.initials: A
authors.lastname: Boumendjel
authors.forename: Chantal
authors.initials: C
authors.lastname: Beney
authors.forename: Nabajyoti
authors.initials: N
authors.lastname: Deka
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mariotte
authors.forename: Martin Ata
authors.initials: MA
authors.lastname: Lawson
authors.forename: Doriane
authors.initials: D
authors.lastname: Trompier
authors.forename: Hélène
authors.initials: H
authors.lastname: Baubichon-Cortay
authors.forename: Attilio
authors.initials: A
authors.lastname: Di Pietro
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003600:Cytosol; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D017434:Protein Structure, Tertiary
chemical_list: C464731:4'-bromo-4-hydroxy-6-methoxyaurone; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001572:Benzofurans