Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
ACS Chem Neurosci. 2013 Jun 19;4(6):924-9. doi: 10.1021/cn400028w. Epub 2013 Mar 21.
The bioactivities of two novel compounds (TAE-1 and TAE-2) that contain a sym-triazine scaffold with acetylcholine-like substitutions are examined as promising candidate agents against Alzheimer's disease. Inhibition of amyloid-β fibril formation in the presence of Aβ1-42, evaluated by Thioflavin T fluorescence, demonstrated comparable or improved activity to a previously reported pentapeptide-based fibrillogenesis inhibitor, iAβ5p. Destabilization of Aβ1-42 assemblies by TAE-1 and TAE-2 was confirmed by scanning electron microscopy imaging. sym-Triazine inhibition of acetylcholinesterase (AChE) activity was observed in cytosol extracted from differentiated human SH-SY5Y neuronal cells and also using human erythrocyte AChE. The sym-triazine derivatives were well tolerated by these cells and promoted beneficial effects on human neurons, upregulating expression of synaptophysin, a synaptic marker protein, and MAP2, a neuronal differentiation marker.
研究了两种含有乙酰胆碱类似取代基的新型化合物（TAE-1 和 TAE-2）的生物活性，它们被认为是对抗阿尔茨海默病的有希望的候选药物。通过噻唑蓝 T 荧光法评估 Aβ1-42 存在下的淀粉样蛋白-β 纤维形成抑制作用，结果表明与先前报道的基于五肽的纤维生成抑制剂 iAβ5p 具有相当或改善的活性。扫描电子显微镜成像证实了 TAE-1 和 TAE-2 对 Aβ1-42 组装体的破坏作用。sym-三嗪对乙酰胆碱酯酶（AChE）活性的抑制作用在分化的人 SH-SY5Y 神经元细胞的细胞质提取物中以及使用人红细胞 AChE 中均有观察到。这些细胞对 sym-三嗪衍生物具有良好的耐受性，并对人神经元产生有益的影响，上调突触小泡蛋白（一种突触标记蛋白）和 MAP2（一种神经元分化标记物）的表达。
