Health Information Technology Department, The Applied College, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Pharmacovigilance and Medication Safety Unit, Centre of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Molecules. 2024 Jan 31;29(3):674. doi: 10.3390/molecules29030674.
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that break down and reduce the level of the neurotransmitter acetylcholine (ACh). This can cause a variety of cognitive and neurological problems, including Alzheimer's disease. Taxifolin is a natural phytochemical generally found in yew tree bark and has significant pharmacological properties, such as being anti-cancer, anti-inflammatory, and antioxidant. The binding affinity and inhibitory potency of taxifolin to these enzymes were evaluated through molecular docking and molecular dynamics simulations followed by the MMPBSA approach, and the results were significant. Taxifolin's affinity for binding to the AChE-taxifolin complex was -8.85 kcal/mol, with an inhibition constant of 326.70 nM. It was observed to interact through hydrogen bonds. In contrast, the BChE-taxifolin complex binding energy was observed to be -7.42 kcal/mol, and it was significantly nearly equal to the standard inhibitor donepezil. The molecular dynamics and simulation signified the observed interactions of taxifolin with the studied enzymes. The MMPBSA total free energy of binding for AChE-taxifolin was -24.34 kcal/mol, while BChE-taxifolin was -16.14 kcal/mol. The present research suggests that taxifolin has a strong ability to bind and inhibit AChE and BChE and could be used to manage neuron-associated problems; however, further research is required to explore taxifolin's neurological therapeutic potential using animal models of Alzheimer's disease.
乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）是分解和降低神经递质乙酰胆碱（ACh）水平的酶。这可能导致各种认知和神经问题，包括阿尔茨海默病。松脂醇是一种天然植物化学物质，通常存在于紫杉树皮中，具有显著的药理学特性，如抗癌、抗炎和抗氧化作用。通过分子对接和分子动力学模拟，再加上 MMPBSA 方法，评估了松脂醇与这些酶的结合亲和力和抑制效力，结果非常显著。松脂醇与 AChE-松脂醇复合物的结合亲和力为-8.85 kcal/mol，抑制常数为 326.70 nM。观察到它通过氢键相互作用。相比之下，BChE-松脂醇复合物的结合能为-7.42 kcal/mol，与标准抑制剂多奈哌齐非常接近。分子动力学和模拟表明观察到了松脂醇与研究酶的相互作用。AChE-松脂醇的 MMPBSA 总结合自由能为-24.34 kcal/mol，而 BChE-松脂醇为-16.14 kcal/mol。本研究表明，松脂醇具有很强的结合和抑制 AChE 和 BChE 的能力，可用于治疗与神经元相关的问题；然而，需要进一步的研究来探索松脂醇在使用阿尔茨海默病动物模型的神经治疗潜力。
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