Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria; Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 9, 1113 Sofia, Bulgaria.
Bioorg Med Chem Lett. 2024 Nov 1;112:129937. doi: 10.1016/j.bmcl.2024.129937. Epub 2024 Aug 30.
Galanthamine derivatives are known for their AChE inhibitory activity. Among them, galanthamine has been approved for treatment of Alzheimer's disease. N-Acetylnorgalanthamine (narcisine) and N-(2'-methyl)allylnorgalanthamine (the most potent natural AChE inhibitor of galanthamine type) were synthetized using N-norgalanthamine as a precursor. The NMR data described previously for narcisine were revised by two-dimensional H-H and H-C chemical shift correlation experiments. AChE inhibitory assays showed that N-acetylnorgalanthamine and N-formylnorgalanthamine (with previously unknown activity) are 4- and 43-times, respectively, less potent than galanthamine. In vitro (AChE inhibitory) and in silico (docking, ADME) assays and comparison of N-(2'-methyl)allylnorgalanthamine with galanthamine prove that this molecule is a very promising natural AChE inhibitor (33-times more potent than galanthamine) which further in vivo studies would provide better estimation about its applicability as a drug.
水仙堿类衍生物因其对乙酰胆碱酯酶的抑制活性而闻名。其中，水仙堿已被批准用于治疗阿尔茨海默病。N-乙酰基水仙堿（那可丁）和 N-（2'-甲基）丙烯基水仙堿（水仙堿型最有效的天然乙酰胆碱酯酶抑制剂）是使用 N-水仙堿作为前体合成的。通过二维 H-H 和 H-C 化学位移相关实验对先前描述的那可丁的 NMR 数据进行了修订。乙酰胆碱酯酶抑制试验表明，N-乙酰基水仙堿和 N-甲酰基水仙堿（具有先前未知的活性）的抑制活性分别比水仙堿低 4 倍和 43 倍。体外（乙酰胆碱酯酶抑制）和计算（对接、ADME）试验以及 N-（2'-甲基）丙烯基水仙堿与水仙堿的比较证明，该分子是一种很有前途的天然乙酰胆碱酯酶抑制剂（比水仙堿强 33 倍），进一步的体内研究将更好地评估其作为药物的适用性。
