Design, synthesis and evaluation of 2-arylethenyl-N-methylquinolinium derivatives as effective multifunctional agents for Alzheimer's disease treatment
| Autor: | Tian-Miao Ou, Chun-Li Xia, Shi-Liang Huang, Zhen-Quan Liu, Honggen Wang, Zhi-Shu Huang, Jia-Qiang Wu, Jia-Heng Tan, Ning Wang, Ding Li, Qian-Liang Guo |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Programmed cell death Antioxidant medicine.medical_treatment 01 natural sciences Antioxidants Cell Line 03 medical and health sciences chemistry.chemical_compound Intragastric administration Alzheimer Disease Drug Discovery medicine Humans Pharmacology Amyloid beta-Peptides Cell Death 010405 organic chemistry Organic Chemistry Quinoline Biological activity General Medicine Glutathione 0104 chemical sciences 030104 developmental biology Alzheimer's disease treatment chemistry Biochemistry Design synthesis Blood-Brain Barrier Drug Design Quinolines Cholinesterase Inhibitors Reactive Oxygen Species |
| Zdroj: | European journal of medicinal chemistry. 130 |
| ISSN: | 1768-3254 |
| Popis: | A series of 2-arylethenyl-N-methylquinolinium derivatives were designed and synthesized based on our previous research of 2-arylethenylquinoline analogues as multifunctional agents for the treatment of Alzheimer's disease (AD) (Eur. J. Med. Chem. 2015, 89, 349–361). The results of in vitro biological activity evaluation, including β-amyloid (Aβ) aggregation inhibition, cholinesterase inhibition, and antioxidant activity, showed that introduction of N-methyl in quinoline ring significantly improved the anti-AD potential of compounds. The optimal compound, compound a12, dramatically attenuated the cell death of glutamate-induced HT22 cells by preventing the generation of ROS and increasing the level of GSH. Most importantly, intragastric administration of a12•HAc was well tolerated at doses up to 2000 mg/kg and could traverse blood-brain barrier. |
| Databáze: | OpenAIRE |
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