Departamento de Química, Universidade Federal de Viçosa, Avenida Peter Henry Rolfs, s/n, Campus Universitário, 36570-900 Viçosa-MG, Brazil.
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Avenida Peter Henry Rolfs, s/n, Campus Universitário, 36570-900 Viçosa-MG, Brazil.
Comput Biol Chem. 2020 Oct;88:107359. doi: 10.1016/j.compbiolchem.2020.107359. Epub 2020 Aug 16.
The present work proposed the preparation of triazolic analogues of tyrosol, a biophenol found in olive oil and whose wide range of bioactivities has been the target of many studies. We obtained fifteen novel tyrosol derivatives and the compounds of the series were later evaluated as acetylcholinesterase (AChE) inhibitors. The study of AChE inhibition is important for the development of new drugs and pesticides, and especially the research for managing Alzheimer's disease. The most active compound, namely 7-({1-[2-(4-hydroxyphenyl)ethyl]-1H-1,2,3-triazol-4-yl}methoxy)-4-methyl-2H-chromen-2-one (30), showed IC value of 14.66 ± 2.29 μmol L. Docking experiments corroborated by kinetic assay are suggestive of a competitive inhibition mechanism. Derivatives interacted with amino acids from the AChE active site associated to the development of Alzheimer's disease. The results indicate that the compounds synthesized have a high potential as prototypes for the development of new acetylcholinesterase inhibitors.
本工作提出了酪氨酸的三唑类似物的制备，酪氨酸是橄榄油中发现的一种生物酚，其广泛的生物活性一直是许多研究的目标。我们获得了十五种新型酪氨酸衍生物，随后对该系列化合物进行了乙酰胆碱酯酶 (AChE) 抑制活性评价。AChE 抑制的研究对于新药物和农药的开发很重要，特别是对阿尔茨海默病的研究。最具活性的化合物，即 7-({1-[2-(4- 羟基苯基)乙基]-1H-1,2,3-三唑-4-基}甲氧基)-4-甲基-2H-色烯-2-酮（30），其 IC 值为 14.66±2.29µmol L。由动力学测定证实的对接实验表明，该化合物的抑制机制为竞争性抑制。这些衍生物与与阿尔茨海默病发病相关的 AChE 活性位点的氨基酸相互作用。结果表明，所合成的化合物具有作为新型乙酰胆碱酯酶抑制剂的原型的高潜力。
