Yerdelen Kadir Ozden, Koca Mehmet, Anil Baris, Sevindik Handan, Kasap Zeynep, Halici Zekai, Turkaydin Kubra, Gunesacar Gulsen
Ataturk University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 25240, Erzurum, Turkey.
Ataturk University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 25240, Erzurum, Turkey.
Bioorg Med Chem Lett. 2015 Dec 1;25(23):5576-82. doi: 10.1016/j.bmcl.2015.10.051. Epub 2015 Oct 20.
Amyloid beta (Aβ) and cholinesterase enzymes (AChE, BuChE) are important biological targets for the effective treatment of Alzheimer's disease. In this study, the aim was to synthesize new donepezil-like secondary amide compounds that display a potent inhibition of cholinesterases and Aβ with antioxidant and metal chelation abilities. All test compounds showed activities against both ChEs and β1-42 inhibition. The most encouraging compound, 20, is an AChE inhibitor with high anti-aggregation activity (55.3%). Based on the results, compound 20 may be a promising structure in further research for new anti-Alzheimer's agents.
β淀粉样蛋白（Aβ）和胆碱酯酶（乙酰胆碱酯酶、丁酰胆碱酯酶）是有效治疗阿尔茨海默病的重要生物学靶点。在本研究中，目标是合成新的多奈哌齐样仲酰胺化合物，这些化合物对胆碱酯酶和Aβ具有强效抑制作用，并具有抗氧化和金属螯合能力。所有测试化合物均显示出对胆碱酯酶和β1-42的抑制活性。最令人鼓舞的化合物20是一种具有高抗聚集活性（55.3%）的乙酰胆碱酯酶抑制剂。基于这些结果，化合物20在新型抗阿尔茨海默病药物的进一步研究中可能是一种有前景的结构。
