Introduction. Alzheimer’s disease (AD) is a neurodegenerative disorder with no conclusive remedy. Yohimbine, found in Rauwolfia vomitoria, may reduce brain inflammation by targeting tumour necrosis factor-alpha (TNFα), implicated in AD pathogenesis. Metoserpate, a synthetic compound, may inhibit TNFα. The study is aimed at assessing the potential utility of repurposing metoserpate for TNFα inhibition to reduce neuronal damage and inflammation in AD. The development of safe and effective treatments for AD is crucial to address the growing burden of the disease, which is projected to double over the next two decades. Methods. Our study repurposed an FDA-approved drug as TNFα inhibitor for AD management using structural similarity studies, molecular docking, and molecular dynamics simulations. Yohimbine was used as a reference compound. Molecular docking used SeeSAR, and molecular dynamics simulation used GROMACS. Results. Metoserpate was selected from 10 compounds similar to yohimbine based on pharmacokinetic properties and FDA approval status. Molecular docking and simulation studies showed a stable interaction between metoserpate and TNFα over 100 ns (100000 ps). This suggests a reliable and robust interaction between the protein and ligand, supporting the potential utility of repurposing metoserpate for TNFα inhibition in AD treatment. Conclusion. Our study has identified metoserpate, a previously FDA-approved antihypertensive agent, as a promising candidate for inhibiting TNFα in the management of AD.

中文翻译：

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利用结构相似性对潜在的 TNF-α 结合剂进行计算机模拟鉴定：一种治疗阿尔茨海默病的潜在药物再利用方法

介绍。阿尔茨海默病（AD）是一种神经退行性疾病，目前尚无确定的治疗方法。在呕吐萝芙木中发现的育亨宾可以通过靶向与 AD 发病机制有关的肿瘤坏死因子-α (TNF α ) 来减少脑部炎症。Metoserpate 是一种合成化合物，可以抑制 TNF α。该研究旨在评估重新利用metoserate抑制TNFα以减少AD中神经元损伤和炎症的潜在效用。开发安全有效的 AD 治疗方法对于解决该疾病日益增长的负担至关重要，预计该疾病在未来二十年将翻一番。方法。我们的研究通过结构相似性研究、分子对接和分子动力学模拟，将FDA 批准的药物重新用作 TNF α抑制剂，用于 AD 治疗。使用育亨宾作为参考化合物。分子对接采用SeeSAR，分子动力学模拟采用GROMACS。结果。Metoserpate 是根据药代动力学特性和 FDA 批准状态从 10 种与育亨宾类似的化合物中选出的。分子对接和模拟研究表明，metoserate 和 TNF α之间存在超过 100 ns (100000 ps) 的稳定相互作用。这表明蛋白质和配体之间存在可靠且强大的相互作用，支持在 AD 治疗中重新利用metoserate 抑制 TNF α的潜在用途。结论。我们的研究发现metoserate（一种先前获得 FDA 批准的抗高血压药物）是治疗 AD 时抑制 TNF α的有希望的候选药物。