PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is a common brain disease associated with cognitive impairment and dementia. donepezil, an acetylcholinesterase (AChE) inhibitor drug as a commercial AD drug represents a non-cost-effective treatment with the toxic effects reported. As the prevalence of AD increases, the development of effective therapeutic treatments is urgently required. Laminaria digitata is a brown seaweed claimed to be able to prevent and treat neurodegenerative diseases. Therefore, this study measured and compared the binding affinity and toxicity of seven common phytoconstituents in Laminaria digitata against acetylcholinesterase (AChE) with those of donepezil using a molecular docking approach. The binding free energy values of donepezil, dieckol, eckol, fucodiphlorethol G, 7-Phloroecol, laminaran, alginic acid, and fucoidan with acetylcholinesterase (AChE) were -12.3, -13.5, -10.5, -8,7, -9.7, -8.0, -10.3, and -7.4 kcal/mol. All ligands constantly interacted with the AChE amino acid residues, namely Tyr124. Dieckol, with the strongest and most stable interaction, is classified as class IV toxicity, with an LD50 value of 866 mg/kg. It has aryl hydrocarbon receptor (AhR) and mitochondrial membrane potential (MMP) toxicity at certain doses. Theoretically, based on Lipinski\'s rule, dieckol is likely to have poor absorption and permeation properties; therefore, several considerations during the drug discovery process are needed.
摘要：
阿尔茨海默病(Alzheimer’sdisease,AD)是一种常见的与认知障碍和痴呆相关的脑部疾病。多奈哌齐,乙酰胆碱酯酶(AChE)抑制剂药物作为商业AD药物代表了一种具有毒性作用的非成本效益治疗。随着AD患病率的增加，迫切需要开发有效的治疗方法。海带是一种棕色海藻，声称能够预防和治疗神经退行性疾病。因此,这项研究使用分子对接方法测量并比较了洋带中7种常见植物成分对乙酰胆碱酯酶（AChE）与多奈哌齐的结合亲和力和毒性。多奈哌齐的结合自由能值，Dieckol,eckol,岩藻二苯醚G,7-Phloecol,laminaran,海藻酸，含乙酰胆碱酯酶（AChE）的岩藻依聚糖为-12.3、-13.5、-10.5、-8,7、-9.7、-8.0、-10.3和-7.4kcal/mol。所有配体不断与AChE氨基酸残基相互作用，也就是Tyr124。Dieckol,具有最强和最稳定的相互作用，被归类为IV类毒性，LD50值为866mg/kg。它在一定剂量下具有芳烃受体（AhR）和线粒体膜电位（MMP）毒性。理论上,根据Lipinski的规则,dieckol可能具有较差的吸收和渗透性能；因此，在药物发现过程中需要考虑几个因素。
