Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany.
Biochem Biophys Res Commun. 2011 Jan 28;404(4):935-40. doi: 10.1016/j.bbrc.2010.12.084. Epub 2010 Dec 23.
Scaffold varied quaternized quinine and cinchonidine alkaloid derivatives were evaluated for their selective butyrylcholinesterase (BChE) inhibitory potential. K(i) values were between 0.4-260.5μM (non-competitive inhibition) while corresponding K(i)values to acetylcholinesterase (AChE) ranged from 7.0-400μM exhibiting a 250-fold selectivity for BChE. Docking arrangements (GOLD, PLANT) revealed that the extended aromatic moieties and the quaternized nitrogen of the inhibitors were responsible for specific π-π stacking and π-cation interactions with the choline binding site and the peripheral anionic site of BChE's active site.
支架不同季铵化奎宁和辛可宁生物碱衍生物被评估为其选择性丁酰胆碱酯酶 (BChE) 抑制潜力。Ki 值在 0.4-260.5μM 之间（非竞争性抑制），而相应的 Ki 值乙酰胆碱酯酶 (AChE) 范围从 7.0-400μM，对 BChE 的选择性为 250 倍。对接安排（GOLD、PLANT）表明，抑制剂的扩展芳基部分和季铵化氮负责与 BChE 活性位点的胆碱结合位点和外周阴离子位点的特定 π-π 堆积和 π-阳离子相互作用。
