Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.
Eur J Med Chem. 2010 Mar;45(3):1256-62. doi: 10.1016/j.ejmech.2009.12.033. Epub 2009 Dec 22.
A number of barbituric acids with appropriate substituent at C-5 position were synthesized and investigated for their interactions with p-gp and Mg(2+). Compounds 5, 6, 8-10, 12-14 and 16 increased the basal activity of p-gp by more than 50% at 0.05 muM concentration. Molecular docking indicate a number of H-bond interactions between these molecules and the amino acid residues of ATP binding site of p-gp. These molecules also showed appreciable interactions with Mg(2+), an important component of efflux pump. All the results of these investigations favor the suitability of barbituric acids toward MDR modulation.
合成了一些在 C-5 位置具有适当取代基的巴比妥酸，并研究了它们与 p-糖蛋白和 Mg(2+)的相互作用。化合物 5、6、8-10、12-14 和 16 在 0.05 μM 浓度下使 p-糖蛋白的基础活性增加了 50%以上。分子对接表明，这些分子与 p-糖蛋白的 ATP 结合位点的氨基酸残基之间存在多种氢键相互作用。这些分子还与 Mg(2+)表现出明显的相互作用，Mg(2+)是外排泵的重要组成部分。这些研究的结果都表明，巴比妥酸适合作为 MDR 调节剂。
