Design, synthesis and bioactivity study of N-salicyloyl tryptamine derivatives as multifunctional agents for the treatment of neuroinflammation

	Design, synthesis and bioactivity study of N-salicyloyl tryptamine derivatives as multifunctional agents for the treatment of neuroinflammation
	Fan, Xiaohong; Li, Junfang; Deng, Xuemei; Lu, Yingmei; Feng, Yiyue; Ma, Shumeng; Wen, Huaixiu; Zhao, Quanyi; Tan, Wen; Shi, Tao
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2020
卷号	193
关键词	Combination principle N-salicyloyl tryptamine Neurodegenerative diseases Neuroinflammation Multifunction
英文摘要	Because of the complex etiology in neuroinflammatory process, the design of multifunctional agents is a potent strategy to cure neuroinflammatory diseases including AD and PD. Herein, based on the combination principles, 23 of N-salicyloyl tryptamine derivatives as multifunctional agents were designed and their new application for anti-neuroinflammation was disclosed. In cyclooxygenase assay, two compounds 3 and 16 displayed extremely preferable COX-2 inhibition than N-salicyloyl tryptamine. In LPSinduced C6 and BV2 cell models, some compounds decreased the production of proinflammatory mediators NO, PGE2, TNF-alpha, iNOS, COX-2 and ROS, while increased the production of IL-10. Among them, compound 3 and 16 showed approximately six-fold better inhibition on nitric oxide production than N-salicyloyl tryptamine in C6. Besides, compounds 3, 13 and 16 attenuated the activation of BV2 and C6 cells. More importantly, in vivo, compounds 3 and 16 reduced GFAP and Iba-1 levels in the hippocampus, and displayed neuroprotection in Nissl staining. Besides, both compounds 3 and 16 had high safety (LD50 > 1000 mg/kg). Longer plasma half-life of compounds 3 and 16 than melatonin supported combination strategy. All these results demonstrated that N-salicyloyl tryptamine derivatives are potential anti-neuroinflammation agents for the treatment of neurodegenerative disorder. (c) 2020 Elsevier Masson SAS. All rights reserved.
内容类型	期刊论文
源URL	[http://210.75.249.4/handle/363003/60346]
专题	西北高原生物研究所_中国科学院西北高原生物研究所
推荐引用方式 GB/T 7714	Fan, Xiaohong,Li, Junfang,Deng, Xuemei,et al. Design, synthesis and bioactivity study of N-salicyloyl tryptamine derivatives as multifunctional agents for the treatment of neuroinflammation[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2020,193.
APA	Fan, Xiaohong.,Li, Junfang.,Deng, Xuemei.,Lu, Yingmei.,Feng, Yiyue.,...&Wang, Zhen.(2020).Design, synthesis and bioactivity study of N-salicyloyl tryptamine derivatives as multifunctional agents for the treatment of neuroinflammation.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,193.
MLA	Fan, Xiaohong,et al."Design, synthesis and bioactivity study of N-salicyloyl tryptamine derivatives as multifunctional agents for the treatment of neuroinflammation".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 193(2020).