Muñoz-Nuñez Evelyn, Quiroz-Carreño Soledad, Pastene-Navarrete Edgar, Seigler David S, Céspedes-Acuña Carlos, Martínez Valenzuela Ignacio, Oppliger Muñoz Martina, Salas-Burgos Alexis, Alarcón-Enos Julio
Grupo de Investigación Química y Biotecnología de Productos Naturales Bioactivos, Laboratorio de Síntesis y Biotransformación de Productos Naturales, Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad del Bío-Bío, Chillán 3800708, Chile.
Department of Plant Biology, Herbarium, University of Illinois at Urbana-Champaign, Champaign, IL 61801, USA.
Metabolites. 2022 Jul 20;12(7):668. doi: 10.3390/metabo12070668.
The purpose of this study was to determine the inhibitory capacity of ceanothanes triterpenes isolate from Chilean Rhamnaceae on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Seven ceanothanes triterpenes were isolated from aerial parts of plant material by classical phytochemical methods or prepared by the hemisynthetic method. Structures were determined by the spectroscopic method (1H-NMR and 13C NMR) and mass spectrometry (MS). AChE and BChE activity were determined by the Ellmann method for all compounds. All tested compounds exerted a greater affinity to AChE than to BChE, where compound 3 has an IC50 of 0.126 uM for AChE and of >500 uM to BChE. Kinetic studies indicated that its inhibition was competitive and reversible. According to the molecular coupling and displacement studies of the propidium iodide test, the inhibitory effect of compound 3 would be produced by interaction with the peripheral anionic site (PAS) of AChE. The compounds tested (1−7) showed an important inhibitory activity of AChE, binding to PAS. Therefore, inhibitors that bind to PAS would prevent the formation of the AChE-Aβ complex, constituting a new alternative in the treatment of Alzheimer’s disease (AD).
本研究的目的是确定从智利鼠李科植物中分离出的ceanothanes三萜类化合物对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的抑制能力。通过经典植物化学方法从植物材料的地上部分分离出七种ceanothanes三萜类化合物，或通过半合成方法制备。通过光谱法（1H-NMR和13C NMR）和质谱法（MS）确定其结构。采用Ellmann法测定所有化合物的AChE和BChE活性。所有测试化合物对AChE的亲和力均大于对BChE的亲和力，其中化合物3对AChE的IC50为0.126 μM，对BChE的IC50大于500 μM。动力学研究表明其抑制作用具有竞争性且可逆。根据碘化丙啶试验的分子偶联和置换研究，化合物3的抑制作用可能是通过与AChE的外周阴离子位点（PAS）相互作用产生的。所测试的化合物（1-7）对AChE表现出重要的抑制活性，并与PAS结合。因此，与PAS结合的抑制剂可阻止AChE-Aβ复合物的形成，这构成了治疗阿尔茨海默病（AD）的一种新选择。
