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DOI	10.1016/j.bioorg.2021.105255
	N-salicyloyl tryptamine derivatives as potential therapeutic agents for Alzheimer's disease with neuroprotective effects
	Bai, Yinliang; Liu, Dan; Zhang, Honghua; Wang, Yuying; Wang, Degui; Cai, Hongbin; Wen, Huaixiu; Yuan, Guoqiang; An, Hui; Wang, Yali; Shi, Tao; Wang, Zhen
通讯作者	Shi, T ; Wang, Z (通讯作者)，Lanzhou Univ, Sch Pharm, West Donggang Rd 199, Lanzhou 730000, Peoples R China.
发表日期	2021
ISSN	0045-2068
EISSN	1090-2120
卷号	115
英文摘要	Alzheimer's disease (AD) has become a serious threat to the developed nations with burgeoning patients and annual costs on health care system in modern society. Neuroinflammation, as one of the specific biochemical factors in the progress of neurodegeneration diseases, performs a crucial role in the pathogenesis and development of AD. Therefore, it is of great significance to develop effective anti-neuroinflammatory strategies for the treatment of AD. N-salicyloyl tryptamine derivatives were previously reported and demonstrated that possessed great potential anti-neuroinflammatory effects and favorable blood-brain barrier (BBB) permeation. Herein, a series of novel N-salicyloyl tryptamine derivatives were synthesized and their anti-AD potential was evaluated both in vitro and in vivo. Among them, L7 performed well anti-neuroinflammatory effects and excellent neuroprotective effects, as well as little toxicity. To lucubrate its potential for the treatment of AD, behavior tests including morris water maze (MWM), eight-arm radial maze, open field test and novel object recognition (NOR) test were carried out and the results showed that L7 could remarkably improve A beta-induced cognitive impairment. Moreover, the mechanism of action of L7 on improving A beta-induced AD was preliminarily investigated, and the results uncovered that the neuroprotective effects of L7 was might exerte via intervening A beta-induced pyroptosis through NLRP3-caspase-1-GSDMD axis and ameliorating neuronal apoptosis by mitochondrial apoptosis pathway. Besides, the distribution of A beta plaques in brain tissues were detected by immunohistochemical (IHC) assay and the results indicated that L7 could significantly attenuate the deposition of A beta plaques in the brain.
关键词	CELL-DEATH INFLAMMASOME PYROPTOSIS NEUROINFLAMMATION MICROGLIA MECHANISM APOPTOSIS
英文关键词	Alzheimer's disease (AD); N-salicyloyl tryptamine derivatives; Neuroprotection; Pyroptosis; Apoptosis
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Organic
WOS记录号	WOS:000703549300008
来源期刊	BIOORGANIC CHEMISTRY
来源机构	中国科学院西北生态环境资源研究院
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/254916
作者单位	[Liu, Dan; Zhang, Honghua; Shi, Tao; Wang, Zhen] Lanzhou Univ, Sch Pharm, West Donggang Rd 199, Lanzhou 730000, Peoples R China; [Bai, Yinliang; Wang, Yuying; Wang, Zhen] Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China; [Wang, Zhen] Univ South China, Sch Pharmaceut Sci, Hengyang 421001, Peoples R China; [Bai, Yinliang; Cai, Hongbin; Yuan, Guoqiang; An, Hui; Wang, Yali] Lanzhou Univ, Hosp 2, Lanzhou 730030, Peoples R China; [Wang, Degui] Lanzhou Univ, Sch Basic Med Sci, Dept Anat & Histol, Lanzhou 730030, Peoples R China; [Wen, Huaixiu] Chinese Acad Sci, Northwest Inst Plateau Biol, Xining 810008, Peoples R China
推荐引用方式 GB/T 7714	Bai, Yinliang,Liu, Dan,Zhang, Honghua,et al. N-salicyloyl tryptamine derivatives as potential therapeutic agents for Alzheimer's disease with neuroprotective effects[J]. 中国科学院西北生态环境资源研究院,2021,115.
APA	Bai, Yinliang.,Liu, Dan.,Zhang, Honghua.,Wang, Yuying.,Wang, Degui.,...&Wang, Zhen.(2021).N-salicyloyl tryptamine derivatives as potential therapeutic agents for Alzheimer's disease with neuroprotective effects.BIOORGANIC CHEMISTRY,115.
MLA	Bai, Yinliang,et al."N-salicyloyl tryptamine derivatives as potential therapeutic agents for Alzheimer's disease with neuroprotective effects".BIOORGANIC CHEMISTRY 115(2021).