Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
J Pineal Res. 2010 Aug;49(1):55-9. doi: 10.1111/j.1600-079X.2010.00766.x. Epub 2010 Apr 29.
The inhibition of cholinesterases plays a crucial role in a therapy of neurodegenerative diseases, including Alzheimer's disease. Especially, butyrylcholinesterase (BChE) has recently gained special interest. On the other hand, compounds having antioxidative properties may have a beneficial role in slowing down neurodegeneration processes. To combine these two effects, we synthesized a series of new derivatives of melatonin, which is a strong antioxidant, possessing structural elements essential for the inhibitory activity against cholinesterase. The structure of the new compounds was confirmed by NMR spectroscopy and mass spectrometry, and their activity against cholinesterases was measured in vitro using modified Ellman's method. The compounds obtained showed a high inhibitory activity, together with a strong selectivity against BChE. These results may point at new area of interest in a research on cholinesterase inhibitors.
乙酰胆碱酯酶的抑制在神经退行性疾病（包括阿尔茨海默病）的治疗中起着至关重要的作用。特别是，丁酰胆碱酯酶（BChE）最近引起了特别的关注。另一方面，具有抗氧化特性的化合物可能在减缓神经退行性过程中具有有益的作用。为了结合这两种作用，我们合成了一系列新的褪黑素衍生物，褪黑素是一种强抗氧化剂，具有抑制乙酰胆碱酯酶活性所必需的结构元素。新化合物的结构通过 NMR 光谱和质谱法得到证实，并通过改良的 Ellman 法在体外测量了它们对乙酰胆碱酯酶的活性。得到的化合物表现出高抑制活性，并且对 BChE 具有很强的选择性。这些结果可能为研究乙酰胆碱酯酶抑制剂开辟了新的研究领域。
