Ryu Young Bae, Curtis-Long Marcus J, Kim Jin Hyo, Jeong Seong Hun, Yang Min Suk, Lee Keun Woo, Lee Woo Song, Park Ki Hun
Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University, Jinju 660-701, Republic of Korea.
Bioorg Med Chem Lett. 2008 Dec 1;18(23):6046-9. doi: 10.1016/j.bmcl.2008.10.033. Epub 2008 Oct 11.
Pterocarpans (1-3) and flavanones (4-10) were isolated from Sophora flavescens and screened for their ability to inhibit neuraminidase (an enzyme crucial in the proliferation of the influenza virus). The majority of inhibitors were shown to have IC(50) values of 20 microM or below. Interestingly, pterocarpan 1 emerged as the best inhibitor with an IC(50) of 1.4 microM. We were thus able to prove that the pterocarpan skeleton is a new class of lead structure for neuraminidase inhibitors. Our studies reveal that the IC(50) has a marked dependence upon structure in the case of the pterocarpans but much less so for the flavanones. Kinetic analysis disclosed that all inhibitors are noncompetitive. Our molecular docking experiment resulted that the most potent pterocarpan-derived inhibitor 1 may bind to another binding pocket adjacent to the active site.
从苦参中分离出紫檀烷类化合物（1-3）和黄烷酮类化合物（4-10），并对它们抑制神经氨酸酶（一种在流感病毒增殖中起关键作用的酶）的能力进行了筛选。大多数抑制剂的半数抑制浓度（IC50）值显示在20微摩尔或更低。有趣的是，紫檀烷1成为最佳抑制剂，IC50为1.4微摩尔。因此，我们能够证明紫檀烷骨架是一类新型的神经氨酸酶抑制剂先导结构。我们的研究表明，对于紫檀烷类化合物，IC50对结构有显著依赖性，但对于黄烷酮类化合物则依赖性小得多。动力学分析表明所有抑制剂均为非竞争性的。我们的分子对接实验结果显示，最有效的紫檀烷衍生抑制剂1可能与活性位点相邻的另一个结合口袋结合。
