4-Hydroxy-6-methoxyaurones with high-affinity binding to cytosolic domain of P-glycoprotein.
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.
Boumendjel
Ahcène
A
Laboratory of Pharmacognosy, UMR-CNRS 5063, Grenoble Pharmacy School, La Tronche, France. Ahcene.Boumendjel@ujf-grenoble.fr
Beney
Chantal
C
Deka
Nabajyoti
N
Mariotte
Anne-Marie
AM
Lawson
Martin Ata
MA
Trompier
Doriane
D
Baubichon-Cortay
Hélène
H
Di Pietro
Attilio
A
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
C464731:4'-bromo-4-hydroxy-6-methoxyaurone; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001572:Benzofurans