Heller Lucie, Kahnt Michael, Loesche Anne, Grabandt Patricia, Schwarz Stefan, Brandt Wolfgang, Csuk René
Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Leibniz Institute of Plant Biochemistry, Bioorganic Chemistry, Weinberg 3, 06120 Halle (Saale), Germany.
Eur J Med Chem. 2017 Jan 27;126:652-668. doi: 10.1016/j.ejmech.2016.11.056. Epub 2016 Nov 30.
A set of thirtyfive 30-norlupan derivatives (2-36) was prepared from the natural triterpenoid platanic acid (PA), and the hydroxyl group at C-3, the carboxyl group at C-17 and the carbonyl group at C-20 were modified. These derivatives were tested for their inhibitory activity for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) using Ellman's assay. Extra enzyme kinetic studies were performed. The most active compound was (3β, 20R)-3-acetyloxy-20-amino-30-norlupan-28-oate (32) showing a K value of 0.01 ± 0.003 μM for BChE. This compound proved to be a selective (F = 851), mixed-type inhibitor for BChE.
以天然三萜类化合物白桦脂酸（PA）为原料制备了一组35个30-降羽扇豆烷衍生物（2-36），并对C-3位的羟基、C-17位的羧基和C-20位的羰基进行了修饰。使用埃尔曼分析法对这些衍生物的乙酰胆碱酯酶（AChE，来自电鳗）和丁酰胆碱酯酶（BChE，来自马血清）抑制活性进行了测试。进行了额外的酶动力学研究。活性最高的化合物是（3β，20R）-3-乙酰氧基-20-氨基-30-降羽扇豆烷-28-酸酯（32），其对BChE的K值为0.01±0.003μM。该化合物被证明是一种对BChE有选择性（F = 851）的混合型抑制剂。
