Alzheimeŕs disease (AD) is the most common neurodegenerative disorder, characterized by neuronal loss and cognitive impairment. Currently, very few drugs are available for AD treatment, and a search for new therapeutics is urgently needed. Thus, in the current study, twenty-eight new derivatives of montanine-type Amaryllidaceae alkaloids were synthesized and evaluated for their ability to inhibit human recombinant acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE). Three derivatives (1n, 1o, and 1p) with different substitution patterns demonstrated significant selective inhibitory potency for hAChE (IC₅₀ < 5 µM), and one analog, 1v, showed selective hBuChE inhibition activity (IC₅₀ = 1.73 ± 0.05 µM). The prediction of CNS availability, as disclosed by the BBB score, suggests that the active compounds in this survey should be able pass through the blood–brain barrier (BBB). Cytotoxicity screening and docking studies were carried out for the two most pronounced cholinesterase inhibitors, 1n and 1v.

阿尔茨海默病 (AD) 是最常见的神经退行性疾病，其特征是神经元丢失和认知障碍。目前，可用于AD治疗的药物很少，迫切需要寻找新的治疗方法。因此，在目前的研究中，合成了 28 种褐煤型石蒜科生物碱的新衍生物，并评估了它们抑制人重组乙酰胆碱酯酶 ( h AChE) 和丁酰胆碱酯酶 ( h BuChE) 的能力。具有不同取代模式的三种衍生物（1n、1o和1p）对h AChE（IC ₅₀  < 5 µM）和一种类似物1v表现出显着的选择性抑制效力, 显示出选择性h BuChE 抑制活性 (IC ₅₀  = 1.73 ± 0.05 µM)。正如 BBB 评分所揭示的，对 CNS 可用性的预测表明，本次调查中的活性化合物应该能够通过血脑屏障 (BBB)。对两种最显着的胆碱酯酶抑制剂1n和1v进行了细胞毒性筛选和对接研究。