Du Hongtao, Jiang Xinyu, Ma Meng, Xu Huili, Liu Shuang, Ma Fang
College of Life Science, Xinyang Normal University, Xinyang 464000, China; College of Science, Northwest A&F University, Yangling 712100, Shaanxi Province, China.
College of Life Science, Xinyang Normal University, Xinyang 464000, China.
Bioorg Med Chem Lett. 2020 Dec 15;30(24):127659. doi: 10.1016/j.bmcl.2020.127659. Epub 2020 Oct 31.
A novel series of deoxyvasicinone-tetrahydro-beta-carboline hybrids were synthesized and evaluated as acetylcholinesterase (AChE) and β-amyloid peptide (Aβ) aggregation inhibitors for the treatment of Alzheimer's disease. The results revealed that the derivatives had multifunctional profiles, including AChE inhibition, Aβ aggregation inhibition, and neuroprotective properties. Inspiringly, hybrids 8b and 8d displayed excellent inhibitory activities against hAChE (IC = 0.93 and 1.08 nM, respectively) and Aβ self-aggregation (IC = 19.71 and 2.05 μM, respectively). In addition, 8b and 8d showed low cytotoxicity and good neuroprotective activity against Aβ-induced damage in SH-SY5Y cells.
合成了一系列新型的脱氧瓦西酮-四氢-β-咔啉杂化物，并将其作为乙酰胆碱酯酶（AChE）和β-淀粉样肽（Aβ）聚集抑制剂进行评估，用于治疗阿尔茨海默病。结果表明，这些衍生物具有多功能特性，包括AChE抑制、Aβ聚集抑制和神经保护特性。令人鼓舞的是，杂化物8b和8d对人AChE表现出优异的抑制活性（IC分别为0.93和1.08 nM）以及对Aβ自聚集的抑制活性（IC分别为19.71和2.05 μM）。此外，8b和8d对SH-SY5Y细胞中Aβ诱导的损伤表现出低细胞毒性和良好的神经保护活性。
