2. Academic Validation
  3. Design, synthesis, and biological evaluation of carbamate derivatives of N-salicyloyl tryptamine as multifunctional agents for the treatment of Alzheimer's disease

Design, synthesis, and biological evaluation of carbamate derivatives of N-salicyloyl tryptamine as multifunctional agents for the treatment of Alzheimer's disease

  • Eur J Med Chem. 2022 Feb 5:229:114044. doi: 10.1016/j.ejmech.2021.114044.
Dan Liu 1,  Honghua Zhang 1,  Yuying Wang 2,  Wencheng Liu 1,  Gaofeng Yin 1,  Degui Wang 3,  Junfang Li 1,  Tao Shi 1,  Zhen Wang 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
  • 2 State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.
  • 3 Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730030, China.
  • 4 School of Pharmacy, Lanzhou University, Lanzhou, 730000, China; School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China. Electronic address: zhenw@lzu.edu.cn.
PMID: 34923430 DOI: 10.1016/j.ejmech.2021.114044
Abstract

In this study, we designed, synthesized, and evaluated a series of carbamate derivatives of N-salicyloyl tryptamine as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). After screening the acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitory activities, target compound 1g stood out as a mixed type reversible dual inhibitor of AChE and BChE. In addition, molecular docking studies were conducted to explore the actions on AChE and BChE. The results showed that 1g could decrease the level of pro-inflammatory cytokines NO, iNOS, IL-6, TNF-α, and ROS, increase the level of anti-inflammatory cytokines IL-4, and inhibit the aggregation of Aβ1-42. Moreover, the administration of 1g suppressed the activity of AChE in the brain. In a word, the compound 1g is effective for improving learning and memory behavior, blood-brain barrier permeation, pharmacokinetics, ChE inhibition, and anti-neuroinflammation. It may be considered as a promising multi-functional therapeutic agent for further investigation for the treatment of AD.

Keywords

Acetylcholinesterase and butyrylcholinesterase inhibitor; Alzheimer's disease; Anti-neuroinflammation; Carbamate derivatives of N-salicyloyl tryptamine.

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