Jamal Qazi Mohammad Sajid, Alharbi Ali H, Ahmad Varish, Ahmad Khurshid
Department of Health Informatics, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
King Salman Center for Disability Research, Riyadh, Saudi Arabia.
PLoS One. 2025 Jul 23;20(7):e0328457. doi: 10.1371/journal.pone.0328457. eCollection 2025.
Alzheimer's disease (AD) remains a major neurodegenerative disorder, characterized by cognitive decline alongside functional impairments that affect daily living. Natural therapeutic alternatives have spurred the search for novel inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two well-established targets in AD therapy. This study utilizes an in silico methodology to investigate new cholinesterase inhibitors sourced from Nyctanthes arbor-tristis, a plant known for its abundant bioactive phytochemicals. Through virtual screening, molecular dynamics simulations (MDS), free energy landscape analysis, and ADMET predictions, eight compounds have been identified as potential inhibitors of AChE and/or BChE. These compounds include Apigenin, Arborside-B, Arbortristoside-D, Arbortristoside-E, Nicotiflorin, Arborside-A, Beta-amyrin, and Nyctanthic acid. These compounds exhibited robust binding affinities compared to the control, advantageous ADMET profiles, and sustained stability throughout 200 ns of MDS and energy assessments, highlighting their potential as viable drug candidates for further exploration. Further experimental studies are required to validate their therapeutic efficacies, thereby confirming their potential as neurological therapeutics for the treatment of AD and related disabilities.
阿尔茨海默病（AD）仍然是一种主要的神经退行性疾病，其特征是认知能力下降以及影响日常生活的功能障碍。天然治疗替代方案促使人们寻找针对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的新型抑制剂，这两种酶是AD治疗中已确立的靶点。本研究利用计算机模拟方法，研究从夜花树（Nyctanthes arbor-tristis）中提取的新型胆碱酯酶抑制剂，该植物以其丰富的具有生物活性的植物化学物质而闻名。通过虚拟筛选、分子动力学模拟（MDS）、自由能景观分析和ADMET预测，已鉴定出八种化合物作为AChE和/或BChE的潜在抑制剂。这些化合物包括芹菜素、树苷-B、树三糖苷-D、树三糖苷-E、烟花苷、树苷-A、β-香树素和夜花酸。与对照相比，这些化合物表现出强大的结合亲和力、有利的ADMET特性，并且在200纳秒的MDS和能量评估过程中保持稳定，突出了它们作为可行药物候选物进一步探索的潜力。需要进一步的实验研究来验证它们的治疗效果，从而证实它们作为治疗AD和相关残疾的神经治疗药物的潜力。
