B-ring substituted 5,7-dihydroxyflavonols with high-affinity binding to P-glycoprotein responsible for cell multidrug resistance

Bioorg Med Chem Lett. 2001 Jan 8;11(1):75-7. doi: 10.1016/s0960-894x(00)00595-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Binding Sites
  • Chalcone / analogs & derivatives
  • Chalcone / chemistry
  • Chalcone / metabolism
  • Drug Resistance, Multiple*
  • Flavonoids / chemical synthesis*
  • Flavonoids / chemistry
  • Flavonoids / metabolism*
  • Flavonols
  • Fluorescence
  • Kaempferols*
  • Molecular Structure
  • Protein Binding
  • Protein Structure, Tertiary
  • Quercetin / analogs & derivatives*
  • Quercetin / metabolism
  • Recombinant Proteins / metabolism
  • Thermodynamics
  • Tryptophan / chemistry

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Flavonoids
  • Flavonols
  • Kaempferols
  • Recombinant Proteins
  • galangin
  • Chalcone
  • kaempferol
  • Tryptophan
  • Quercetin