Institut de Chimie des Substances Naturelles, Bt 27, CNRS Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Eur J Med Chem. 2011 Jun;46(6):2193-205. doi: 10.1016/j.ejmech.2011.02.073. Epub 2011 Mar 23.
New acetylcholinesterase inhibitors in the tetracyclic triterpene series were synthesized, tested in vitro for the inhibition of cholinesterases (different sources of AChE and BuChE) and for the ability to prevent AChE-induced Aβ aggregation. Some compounds have hAChE IC50 values in the nanomolar range and showed ability to block the AChE-induced Aβ aggregation. The mode of interaction between EeAChE and compounds 1 and 36e was investigated using docking and molecular dynamics simulations. These studies suggested that both compounds interact simultaneously with the catalytic and the peripheral sites of AChE, and the nature of protein-ligand interactions is mainly hydrophobic.
合成了四环三萜系列中的新型乙酰胆碱酯酶抑制剂，对其体外抑制乙酰胆碱酯酶（不同来源的 AChE 和 BuChE）和预防 AChE 诱导的 Aβ聚集的能力进行了测试。一些化合物对 hAChE 的 IC50 值在纳摩尔范围内，并显示出阻止 AChE 诱导的 Aβ聚集的能力。使用对接和分子动力学模拟研究了 EeAChE 与化合物 1 和 36e 之间的相互作用模式。这些研究表明，这两种化合物都同时与 AChE 的催化和外周部位相互作用，并且蛋白质-配体相互作用的性质主要是疏水的。
