Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan, 453007, China; College of Pharmacy, Xinxiang Medical University, China.
Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan, 453007, China.
Carbohydr Res. 2020 May;491:107977. doi: 10.1016/j.carres.2020.107977. Epub 2020 Mar 5.
Based on structure analyses of butyrylcholinesterase (BChE), a series of 21 acridone glycosides were designed, synthesized and evaluated in vitro for their BChE and acetylcholinesterase (AChE) inhibitory activities. d-ribose derivative 6f exhibited the greatest inhibitory activity on BChE (IC = 6.95 μM), and was the most selective inhibitor of BChE with the IC ratio of AChE/BChE was 20.59. d-glucose and d-galactose derivatives 6a and 6b showed inhibitory activities against both AChE and BChE. Moreover, compounds 6a, 6b, 6f and 5t were found nontoxic on SHSY5Y neuroblastoma and HepG2 cell and exhibited remarkable neuroprotective activity. Besides, compound 6f showed mixed-type inhibition against BChE (K = 1.76 μM), which renders 6f a potential agent for the treatment of Alzheimer's disease. These novel acridone hybrids might be used as efficient probes to reveal the relationship between ligands and BChE and pave the way for developing selective BChE inhibitors to further study the pathogenesis of alzheimer's disease.
基于丁酰胆碱酯酶（BChE）的结构分析，设计、合成了一系列 21 种吖啶酮糖苷，并对其体外抑制 BChE 和乙酰胆碱酯酶（AChE）的活性进行了评价。d-核糖衍生物 6f 对 BChE 的抑制活性最大（IC = 6.95 μM），是 BChE 最具选择性的抑制剂，AChE/BChE 的 IC 比值为 20.59。d-葡萄糖和 d-半乳糖衍生物 6a 和 6b 对 AChE 和 BChE 均有抑制作用。此外，化合物 6a、6b、6f 和 5t 对 SHSY5Y 神经母细胞瘤和 HepG2 细胞均无毒性，并表现出显著的神经保护活性。此外，化合物 6f 对 BChE 表现出混合型抑制（K = 1.76 μM），这使得 6f 成为治疗阿尔茨海默病的潜在药物。这些新型吖啶酮杂合体可能被用作有效的探针，以揭示配体与 BChE 之间的关系，并为开发选择性 BChE 抑制剂以进一步研究阿尔茨海默病的发病机制铺平道路。
