ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Department of Bioorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Bioorg Chem. 2021 Feb;107:104567. doi: 10.1016/j.bioorg.2020.104567. Epub 2020 Dec 19.
Twenty known Amaryllidaceae alkaloids of various structural types, and one undescribed alkaloid of narcikachnine-type, named narcieliine (3), have been isolated from fresh bulbs of Zephyranthes citrina. The chemical structures of the isolated alkaloids were elucidated by a combination of MS, HRMS, 1D and 2D NMR, and CD spectroscopic techniques, and by comparison with literature data. The absolute configuration of narcieliine (3) has also been determined. Compounds isolated in a sufficient quantity were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; E.C. 3.1.1.8), and prolyl oligopeptidase (POP; E.C. 3.4.21.26) inhibition activities. Significant human AChE/BuChE (hAChE/hBuChE) inhibitory activity was demonstrated by the newly described alkaloid narcieliine (3), with IC values of 18.7 ± 2.3 µM and 1.34 ± 0.31 µM, respectively. This compound is also predicted to cross the blood-brain barrier (BBB) through passive diffusion. The in vitro data were further supported by in silico studies of 3 in the active site of hAChE/hBuChE.
从黄花葱属植物新鲜鳞茎中分离得到了 20 种结构类型各异的石蒜科生物碱和 1 种结构未知的纳曲林型生物碱，命名为纳氏碱（3）。通过 MS、HRMS、1D 和 2D NMR、CD 光谱技术以及与文献数据的比较，阐明了分离得到的生物碱的化学结构。还确定了纳氏碱（3）的绝对构型。分离得到足够数量的化合物用于评估其对体外乙酰胆碱酯酶（AChE；E.C. 3.1.1.7）、丁酰胆碱酯酶（BuChE；E.C. 3.1.1.8）和脯氨酰寡肽酶（POP；E.C. 3.4.21.26）抑制活性。新描述的生物碱纳氏碱（3）对人乙酰胆碱酯酶/丁酰胆碱酯酶（hAChE/hBuChE）具有显著的抑制活性，IC 值分别为 18.7 ± 2.3 μM 和 1.34 ± 0.31 μM。该化合物也被预测可以通过被动扩散穿过血脑屏障（BBB）。体外数据进一步得到了 3 在 hAChE/hBuChE 活性部位的计算机模拟研究的支持。
