a Laboratoire de Pharmacognosie-UFR de Pharmacie de Grenoble,Université Joseph Fourier, 38706, La Tronche, France
b Institut de Biologie et Chimie des Protéines, UPR 412-CNRS, 7 Passage du Vercors, 69367, Lyon Cedex 07, France
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 goups 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 KD of 20 nM was obtained.