ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy , Charles University , Heyrovskeho 1203 , 500 05 Hradec Kralove , Czech Republic.
Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy , Charles University , Heyrovskeho 1203 , 500 05 Hradec Kralove , Czech Republic.
J Nat Prod. 2019 Feb 22;82(2):239-248. doi: 10.1021/acs.jnatprod.8b00592. Epub 2019 Jan 31.
Three new alkaloids, bersavine (3), muraricine (4), and berbostrejdine (8), together with seven known isoquinoline alkaloids (1-2, 5-7, 9, and 10) were isolated from an alkaloidal extract of the root bark of Berberis vulgaris. The structures of the isolated compounds were determined by spectroscopic methods, including 1D and 2D NMR techniques, HRMS, and optical rotation, and by comparison of the obtained data with those in the literature. The NMR data of berbamine (5), aromoline (6), and obamegine (7) were completely assigned employing 2D NMR experiments. Alkaloids isolated in sufficient amounts were evaluated for their in vitro acetylcholinesterase, butyrylcholinesterase (BuChE), prolyl oligopeptidase, and glycogen synthase kinase-3β inhibitory activities. Selected compounds were studied for their ability to permeate through the blood-brain barrier. Significant human BuChE ( hBuChE) inhibitory activity was demonstrated by 6 (IC = 0.82 ± 0.10 μM). The in vitro data were further supported by computational analysis that showed the accommodation of 6 in the active site of hBuChE.
从小檗属植物的根皮的生物碱提取物中分离得到了三个新的生物碱，分别为 bersavine（3）、muraricine（4）和 berbostrejdine（8），以及 7 种已知的异喹啉生物碱（1-2、5-7、9 和 10）。通过光谱方法，包括 1D 和 2D NMR 技术、高分辨质谱和旋光，以及与文献数据的比较，确定了分离化合物的结构。采用 2D NMR 实验完全确定了 berbamine（5）、aromoline（6）和 obamegine（7）的 NMR 数据。分离得到的足够数量的生物碱用于评估其体外乙酰胆碱酯酶、丁酰胆碱酯酶（BuChE）、脯氨酰寡肽酶和糖原合酶激酶-3β抑制活性。对选定的化合物进行了穿透血脑屏障的能力研究。化合物 6（IC=0.82±0.10μM）对人丁酰胆碱酯酶（hBuChE）具有显著的抑制活性。体外数据得到了计算分析的进一步支持，表明 6 能够容纳在 hBuChE 的活性部位中。
