Bois F, Boumendjel A, Mariotte A M, Conseil G, Di Petro A
Laboratoire de Pharmacognosie-UFR de Pharmacie de Grenoble, Université Joseph Fourier, La Tronche, France.
Bioorg Med Chem. 1999 Dec;7(12):2691-5. doi: 10.1016/s0968-0896(99)00218-7.
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.
已经合成了一系列4-烷氧基-2',4',6'-三羟基查尔酮，并评估了它们通过直接结合包含ATP结合位点和调节剂相互作用区域的纯化蛋白结构域来抑制P-糖蛋白介导的多药耐药性（MDR）的能力。与母体查尔酮相比，在4位引入疏水烷氧基导致活性更高的化合物。结合亲和力随链长增加而增加，直至获得K(D)为20 nM的辛氧基衍生物。
