Departamento de Ciencias Básicas, Universidad del Bío-Bío, Chillán, Chile.
Instituto de Química, Universidad de Talca, Talca, Chile.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):1845-1856. doi: 10.1080/14756366.2022.2091554.
In order to find molecules of natural origin with potential biological activities, we isolate and synthesise compounds with agarofuran skeletons (epoxyeudesmanes). From the seeds of and we obtained six dihydro-β-agarofurans, and by means of the Robinson annulation reaction we synthesised five compounds with the same skeleton. The structures were established on the basis of NMR, IR, and MS. The evaluated compounds showed inhibitory activity on the acetylcholinesterase enzyme and on the COX enzymes. Compound emerged as the most potent in the acetylcholinesterase inhibition assay with IC 17.0 ± 0.016 µM on acetylcholinesterase (AChE). The compounds evaluated were shown to be selective for AChE. The molecular docking, and the propidium displacement assay suggested that the compounds do not bind to the active site of the enzyme AChE, but rather bind to the peripheral anionic site (PAS) of the enzyme, on the other hand, the natural compound , showed the best inhibitory activity on the COX-2 enzyme with an IC value of 0.04 ± 0.007 µM. The pharmacokinetic profile calculated in silico using the SWISSADME platform shows that these molecules could be considered as potential drugs for the treatment of neurodegenerative diseases such as AD.
为了寻找具有潜在生物活性的天然来源分子，我们分离并合成了具有agarofuran 骨架（环氧桉烷）的化合物。我们从 和 的种子中获得了六个二氢-β-agarofurans，并通过 Robinson 环化反应合成了具有相同骨架的五个化合物。结构是基于 NMR、IR 和 MS 确定的。评估的化合物对乙酰胆碱酯酶和 COX 酶表现出抑制活性。化合物 在乙酰胆碱酯酶抑制试验中表现出最强的抑制活性，对乙酰胆碱酯酶 (AChE) 的 IC 17.0 ± 0.016 µM。评估的化合物对 AChE 具有选择性。分子对接和碘化丙啶置换试验表明，这些化合物不与酶 AChE 的活性位点结合，而是与酶的外周阴离子位点 (PAS) 结合，另一方面，天然化合物 对 COX-2 酶表现出最好的抑制活性，IC 值为 0.04 ± 0.007 µM。使用 SWISSADME 平台在计算机上计算的药代动力学特征表明，这些分子可被视为治疗 AD 等神经退行性疾病的潜在药物。
