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2-羟基亚氨基乙酮作为抗炎和β-淀粉样蛋白聚集抑制剂的合成及生物学评价

Synthesis and Biological Assessment of 2-Hydroxyiminoethanones as Anti-Inflammatory and β-Amyloid Aggregation Inhibitors.

作者信息

Valipour Mehdi, Davaji Issa, Abedi Niusha, Rajabi Mahsa, Küçükkılınç Tuba Tüylü, Ayazgök Beyza, Irannejad Hamid

机构信息

Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Iran J Pharm Res. 2019 Summer;18(3):1288-1298. doi: 10.22037/ijpr.2019.15567.13181.

Abstract

Alzheimer's disease (AD) is a neuroinflammatory based pathologic state in which β-amyloid aggregates are major devastating agents. In this study, a series of 2-hydroxyiminoethanones were synthesized and evaluated as anti-inflammatory in carrageenan and formalin tests and inhibitors of β-amyloid aggregation. Compounds were synthesized through a two-step reaction. Results: Compounds showed more β-amyloid disaggregation ability than reference drugs rifampicin and donepezil and compound was the best compound in this series and could reduce the extent of amyloid aggregation to 50.9%. Interestingly, compounds and showed significant anti-inflammatory activity in carrageenan-induced paw edema compared to control group and equivalent to the reference drug indomethacin. 2-Hydeoxyiminoethanones are privileged scaffold for further drug research and development as anti-neuroinflammatory and neuroprotective agents.

摘要

阿尔茨海默病(AD)是一种基于神经炎症的病理状态,其中β-淀粉样蛋白聚集体是主要的破坏因子。在本研究中,合成了一系列2-羟基亚氨基乙酮,并在角叉菜胶和福尔马林试验中评估其抗炎活性以及作为β-淀粉样蛋白聚集抑制剂的活性。化合物通过两步反应合成。结果:化合物显示出比参考药物利福平和多奈哌齐更强的β-淀粉样蛋白解聚能力,化合物是该系列中最佳的化合物,可将淀粉样蛋白聚集程度降低至50.9%。有趣的是,与对照组相比,化合物和在角叉菜胶诱导的爪肿胀中显示出显著的抗炎活性,且与参考药物吲哚美辛相当。2-脱氧亚氨基乙酮是作为抗神经炎症和神经保护剂进行进一步药物研发的优势骨架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fb4/6934981/5ecafb2d437e/ijpr-18-1288-g001.jpg

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