Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad 747424, Pakistan.
State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen 518000, China.
Biomolecules. 2020 Mar 13;10(3):443. doi: 10.3390/biom10030443.
Oxidative stress-mediated neuroinflammatory events are the hallmark of neurodegenerative diseases. The current study aimed to synthesize a series of novel succinamide derivatives and to further investigate the neuroprotective potential of these compounds against scopolamine-induced neuronal injury by in silico, morphological, and biochemical approaches. The characterization of all the succinamide derivatives was carried out spectroscopically via proton NMR (H-NMR), FTIR and elemental analysis. Further in vivo experiments showed that scopolamine induced neuronal injury, characterized by downregulated glutathione (GSH), glutathione S-transferase (GST), catalase, and upregulated lipid peroxidation (LPO). Moreover, scopolamine increased the expression of inflammatory mediators such as cyclooxygenase2 (COX2), nuclear factor kappa B (NF-kB), tumor necrosis factor (TNF-α), further associated with cognitive impairment. On the other hand, treatment with succinamide derivatives ameliorated the biochemical and immunohistochemical alterations induced by scopolamine, further supported by the results obtained from molecular docking and binding affinities.
氧化应激介导的神经炎症事件是神经退行性疾病的标志。本研究旨在合成一系列新型琥珀酰胺衍生物，并通过计算机模拟、形态学和生化方法进一步研究这些化合物对东莨菪碱诱导的神经元损伤的神经保护潜力。所有琥珀酰胺衍生物的特性均通过质子 NMR（H-NMR）、FTIR 和元素分析进行光谱鉴定。进一步的体内实验表明，东莨菪碱诱导神经元损伤，表现为谷胱甘肽（GSH）、谷胱甘肽 S-转移酶（GST）、过氧化氢酶下调，脂质过氧化（LPO）上调。此外，东莨菪碱增加了炎症介质的表达，如环氧化酶 2（COX2）、核因子 kappa B（NF-kB）、肿瘤坏死因子（TNF-α），进一步与认知障碍相关。另一方面，琥珀酰胺衍生物治疗改善了东莨菪碱诱导的生化和免疫组织化学改变，这一结果得到了分子对接和结合亲和力结果的支持。
