Title
Design, synthesis and evaluation of 2-arylethenyl-N-methylquinolinium derivatives as effective multifunctional agents for Alzheimer’s disease treatment
Author
Chun-Li Xia, Ning Wang, Qian-Liang Guo, Zhen-Quan Liu, Jia-Qiang Wu, Shi-Liang Huang, Tian-Miao Ou, Jia-Heng Tan, Hong-Gen Wang, Ding Li, Zhi-Shu Huang
Year
2017
Journal
European Journal of Medicinal Chemistry
Abstract
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.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Aggregation, Biochemistry