Bois F, Beney C, Boumendjel A, Mariotte A M, Conseil G, Di Pietro A
Laboratoire de Pharmacognosie, UFR de Pharmacie de Grenoble, Université Joseph Fourier, 38706 La Tronche, France.
J Med Chem. 1998 Oct 8;41(21):4161-4. doi: 10.1021/jm9810194.
Previous studies have shown that flavonoids are modulators of the transmembrane P-glycoprotein (P-gp) which mediates cell multidrug resistance. Some structural elements have been identified which seem to contribute to these compounds' activity. In the present study, a series of halogenated chalcones was prepared to further explore the structural requirements for the P-gp modulation. Four halogenated chalcones have been synthesized and evaluated as potential modulators of P-gp-mediated multidrug resistance of cancer cells by in vitro assays using a purified recombinant domain of the transporter containing the modulator binding site. Halogenated chalcones exhibited high-affinity binding, the 2',4', 6'-trihydroxy-4-iodochalcone behaving as the most potent compound with a KD value in the nanomolar range.
先前的研究表明，黄酮类化合物是跨膜P-糖蛋白（P-gp）的调节剂，P-糖蛋白介导细胞多药耐药性。已经确定了一些似乎有助于这些化合物活性的结构元件。在本研究中，制备了一系列卤代查耳酮，以进一步探索P-糖蛋白调节的结构要求。通过使用含有调节剂结合位点的转运蛋白的纯化重组结构域进行体外测定，合成并评估了四种卤代查耳酮作为P-糖蛋白介导的癌细胞多药耐药性的潜在调节剂。卤代查耳酮表现出高亲和力结合，2'，4'，6'-三羟基-4-碘查耳酮是最有效的化合物，KD值在纳摩尔范围内。
