B-ring substituted 5,7-dihydroxyflavonols with high-affinity binding to P-glycoprotein responsible for cell multidrug resistance.
Starting from the interaction of galangin (3,5,7-trihydroxyflavone) with a cytosolic nucleotide-binding domain of P-glycoprotein, a series of flavonol derivatives was synthesized and tested for their binding affinity towards the same target. The 5,7-dihydroxy-4'-iodoflavonol and 5,7-dihydroxy-4'-n-octylflavonol derivatives displayed much higher binding affinities, with respective increases of 6- and 93-fold as compared to galangin.
Boumendjel
A
A
Département de Pharmacochimie Moléculaire UMR-CNRS 5063, UFR de Pharmacie de Grenoble, La Tronche, France. ahcene.boumendjel@ujf-grenoble.fr
Bois
F
F
Beney
C
C
Mariotte
A M
AM
Conseil
G
G
Di Pietro
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002599:Chalcone / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D018432:Drug Resistance, Multiple; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D044948:Flavonols; D005453:Fluorescence; D044949:Kaempferols; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids; D044948:Flavonols; D044949:Kaempferols; D011994:Recombinant Proteins; C037032:galangin; D002599:Chalcone; C006552:kaempferol; D014364:Tryptophan; D011794:Quercetin