当前位置: X-MOL 学术Drug Des. Dev. Ther. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Synthesis and Bioactivity Evaluation of a Novel 1,2,4-Oxadiazole Derivative in vitro and in 3×Tg Mice
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2022-09-25 , DOI: 10.2147/dddt.s372750
Zhuohui Luo 1 , Yongcheng Wang 2 , Shuo Pang 1 , Shan Gao 1 , Ning Liu 1 , Xiang Gao 1 , Li Zhang 1, 3 , Xiaolong Qi 1, 3 , Yajun Yang 2 , Lianfeng Zhang 1, 3
Affiliation  

Aim: 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.
Purpose: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: wyc-7-20 was potent in AD therapy.
Graphical abstract:

Keywords: 1,2,4-oxadiazole, Alzheimer’s disease, animal model, neuroprotective effect


中文翻译:

一种新型 1,2,4-恶二唑衍生物在体外和 3×Tg 小鼠中的合成和生物活性评价

目的: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,合成了一种新型的 1,2,4-恶二唑衍生物 wyc-7-20,它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,在转基因动物模型中检测到改善的认知障碍、β-淀粉样蛋白 (Aβ) 清除和 tau 病理表型。还检测到 AD 相关基因的反向表达。结果表明 wyc-7-20 在 AD 治疗中是有效的。
目的:AD的病理复杂性增加了医学研究的难度。为了探索治疗 AD 的新的潜在药物,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。
材料与方法:人神经母细胞瘤(SH-SY5Y)细胞和人肝细胞癌(HepG2)细胞用于检测中位致死剂量(LD50)。H 2 O 2和 Aβ 1– 42将寡聚体(AβOs)分别添加到SH-SY5Y细胞中以检测wyc-7-20的抗ROS(活性氧)和抗AβOs作用。给3×Tg小鼠施用wyc-7-20,然后应用Y迷宫试验和Morris水迷宫(MWM)试验检测认知改善。随后使用不同的技术收集和分析脑组织样本。
结果: 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,在转基因动物模型中检测到改善的认知障碍、Aβ 清除和 tau 病理表型。还检测到 AD 相关基因的反向表达。
结论: wyc-7-20 在 AD 治疗中是有效的。
图形摘要:

关键词:1,2,4-恶二唑,阿尔茨海默病,动物模型,神经保护作用
更新日期:2022-09-24
down
wechat
bug