Synthesis and Bioactivity Evaluation of a Novel 1,2,4-Oxadiazole Derivative in vitro and in 3×Tg Mice.
Synthesis and Bioactivity Evaluation of a Novel 1,2,4-Oxadiazole Derivative in vitro and in 3×Tg Mice.
复制标题
新型 1,2,4-恶二唑衍生物的体外合成和生物活性评价以及 3×Tg 小鼠体内的生物活性评价。
DOI：
10.2147/dddt.s372750
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
阿尔茨海默病（AD）是最常见的神经退行性疾病，患者患有认知障碍。在我们的研究中，合成了一种新型1,2,4-恶二唑衍生物wyc-7-20，其在细胞水平上表现出低细胞毒性和有效的神经保护作用。在 wyc-7-20 治疗后，转基因动物模型中检测到认知障碍、β-淀粉样蛋白 (Aβ) 清除率和 tau 病理表型得到改善。还检测到 AD 相关基因的反向表达。结果表明 wyc-7-20 在 AD 治疗中有效。 AD病理的复杂性增加了医学研究的难度。为了探索治疗 AD 的新的潜在医学治疗方法，设计合成了一种新型 1,2,4-恶二唑衍生物 (wyc-7-20)，以探索在本研究中的应用。采用人神经母细胞瘤（SH-SY5Y）细胞和人肝细胞癌（HepG2）细胞检测半数致死剂量（LD50）。将H2O2和Aβ1-42寡聚物（AβOs）分别添加到SH-SY5Y细胞中，检测wyc-7-20的抗ROS（活性氧）和抗AβOs作用。 3×Tg小鼠给予wyc-7-20，然后应用Y迷宫测试和Morris水迷宫（MWM）测试来检测认知改善。随后使用不同的技术收集并分析脑组织样本。 wyc-7-20 在细胞水平上表现出低细胞毒性和有效的神经保护作用。在 wyc-7-20 治疗后，转基因动物模型中检测到认知障碍、Aβ 清除率和 tau 病理表型得到改善。还检测到 AD 相关基因的反向表达。 wyc-7-20 在 AD 治疗中有效。
Alzheimer’s disease (AD) is the most common neurodegenerative disease whose patients suffered from cognitive impairments. In our study, a novel 1,2,4-Oxadiazole derivative wyc-7-20 was synthesized, which showed low cytotoxicity and potent neuroprotective effect at the cellular level. Improved cognitive impairments, β-amyloid (Aβ) clearance, and tau pathological phenotypes were detected in transgenic animal models after wyc-7-20 treatment. Reversed expressions in AD-related genes were also detected. The results demonstrated wyc-7-20 was potent in AD therapy. The pathological complexity of AD increased difficulties in medical research. To explore a new potential medical treatment for AD, a novel 1,2,4-Oxadiazole derivative (wyc-7-20) was designed, synthesized to explore the application in this study. Human neuroblastoma (SH-SY5Y) cells and human hepatocellular carcinoma (HepG2) cells were used to detect median lethal dose (LD50). H2O2 and Aβ1–42 oligomers (AβOs) were respectively, added into SH-SY5Y cells to detect anti-ROS (reactive oxygen species) and anti-AβOs effects of wyc-7-20. 3×Tg mice were administered with wyc-7-20, and then Y maze test and Morris water maze (MWM) test were applied to detect cognitive improvements. Brain tissue samples were subsequently collected and analyzed using different techniques. wyc-7-20 showed low cytotoxicity and potent neuroprotective effect at the cellular level. Improved cognitive impairments, Aβ clearance, and tau pathological phenotypes were detected in transgenic animal models after wyc-7-20 treatment. Reversed expressions in AD-related genes were also detected. wyc-7-20 was potent in AD therapy.