Synthesis and biological activity of 4-alkoxy chalcones: potential hydrophobic modulators of P-glycoprotein-mediated multidrug resistance

F Bois; A Boumendjel; A M Mariotte; G Conseil; A Di Petro

doi:10.1016/s0968-0896(99)00218-7

Synthesis and biological activity of 4-alkoxy chalcones: potential hydrophobic modulators of P-glycoprotein-mediated multidrug resistance

Bioorg Med Chem. 1999 Dec;7(12):2691-5. doi: 10.1016/s0968-0896(99)00218-7.

Authors

F Bois¹, A Boumendjel, A M Mariotte, G Conseil, A Di Petro

Affiliation

¹ Laboratoire de Pharmacognosie-UFR de Pharmacie de Grenoble, Université Joseph Fourier, La Tronche, France.

PMID: 10658573
DOI: 10.1016/s0968-0896(99)00218-7

Abstract

A series of 4-alkoxy-2',4',6'-trihydroxychalcones have been synthesized and evaluated for their ability to inhibit P-glycoprotein-mediated multidrug resistance (MDR) by direct binding to a purified protein domain containing an ATP-binding site and a modulator-interacting region. The introduction of hydrophobic alkoxy groups at position 4 led to much more active compounds as compared to the parent chalcone. The binding affinity increased as a function of the chain length, up to the octyloxy derivative for which a K(D) of 20 nM was obtained.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Adenosine Triphosphate / metabolism
Animals
Binding Sites
Chalcone / analogs & derivatives*
Chalcone / chemical synthesis
Chalcone / pharmacology
Drug Evaluation, Preclinical
Drug Resistance, Multiple / physiology*
In Vitro Techniques
Magnetic Resonance Spectroscopy
Protein Binding
Protein Structure, Tertiary
Rabbits
Structure-Activity Relationship

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Chalcone
Adenosine Triphosphate