Facultad de Química, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Casilla 306, Correo 22, Santiago, Chile.
Bioorg Med Chem. 2012 Jun 15;20(12):3719-27. doi: 10.1016/j.bmc.2012.04.050. Epub 2012 May 2.
In this study thirty-three novel indole derivatives were designed and synthesized based on the structure of deformylflustrabromine B (1), a metabolite isolated from the marine bryozoan Flustra foliacea L. The syntheses were carried out using standard methodologies and in good yields. The molecules were tested for their affinities for the α4β2(∗), α3β4(∗), α7(∗) and (α1)(2)β1γδ nicotinic acetylcholine receptor (nAChR) subtypes. Binding assays showed that, among these ligands, compound 7c exhibited the highest affinity with K(i)=136.1, 93.9 and 862.4nM for the α4β2(∗), α3β4(∗), and α7(∗) nAChRs subtypes, respectively. These results indicated that the indole core might be a useful scaffold for the development of new potent and selective nAChR ligands.
在这项研究中，基于从海洋苔藓虫 Flustra foliacea L 中分离出的代谢产物变形氟溴虫 B（1）的结构，设计并合成了 33 种新型吲哚衍生物。合成采用标准方法进行，产率良好。这些分子被测试了它们对α4β2（）、α3β4（）、α7（）和（α1）（2）β1γδ 烟碱型乙酰胆碱受体（nAChR）亚型的亲和力。结合实验表明，在这些配体中，化合物 7c 对α4β2（）、α3β4（）和 α7（）nAChR 亚型的亲和力最高，Ki 值分别为 136.1、93.9 和 862.4 nM。这些结果表明，吲哚核心可能是开发新型有效和选择性 nAChR 配体的有用支架。
