Milisavljević Kristina, Milanović Žiko, Matić Jovana, Antonijević Marko, Simić Vladimir, Milošević Miljan, Kosanić Marijana, Kaluđerović Goran N
Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia.
Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia.
Nanomaterials (Basel). 2025 Jun 12;15(12):914. doi: 10.3390/nano15120914.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction and neuronal loss due to the accumulation of amyloid-β peptides and tau proteins. In the pursuit of novel neuroprotective strategies, organotin(IV) compounds have garnered attention due to their unique chemical and biological properties. This study evaluates the inhibitory potential of two triphenyltin(IV) derivatives-(3-propan-1-ol)triphenyltin(IV) () and (4-butan-1-ol)triphenyltin(IV) ()-in both free form and immobilized into mesoporous silica SBA-15~Cl, targeting acetylcholinesterase (), a key enzyme involved in AD pathophysiology. The nanostructures exhibited the most potent inhibitory activity against (IC = 0.58 μM), significantly outperforming the standard drug galantamine. Molecular docking, molecular dynamics simulations, and MM/GBSA and MM/PBSA analyses confirmed the stability and selectivity of interactions with , primarily driven by hydrophobic interactions. Compound transport was also simulated using a multi-scale 3D mouse brain model to evaluate brain tissue distribution and blood-brain barrier permeability. The results highlight the strong potential of SBA-15-loaded organotin(IV) compounds as biocompatible neuroprotective agents for novel treatments of neurodegenerative diseases.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是由于淀粉样β肽和tau蛋白的积累导致突触功能障碍和神经元丧失。在寻求新型神经保护策略的过程中，有机锡（IV）化合物因其独特的化学和生物学特性而受到关注。本研究评估了两种三苯基锡（IV）衍生物——（3-丙醇）三苯基锡（IV）（）和（4-丁醇）三苯基锡（IV）（）——以游离形式以及固定在介孔二氧化硅SBA-15~Cl中的形式，针对乙酰胆碱酯酶（）的抑制潜力，乙酰胆碱酯酶是AD病理生理学中的一种关键酶。该纳米结构对乙酰胆碱酯酶表现出最有效的抑制活性（IC = 0.58 μM），显著优于标准药物加兰他敏。分子对接、分子动力学模拟以及MM/GBSA和MM/PBSA分析证实了与乙酰胆碱酯酶相互作用的稳定性和选择性，主要由疏水相互作用驱动。还使用多尺度三维小鼠脑模型模拟了化合物转运，以评估脑组织分布和血脑屏障通透性。结果突出了负载SBA-15的有机锡（IV）化合物作为生物相容性神经保护剂用于神经退行性疾病新治疗的强大潜力。
