Inhibition of acetylcholinesterase activity and β-amyloid oligomer formation by 6-bromotryptamine A, a multi-target anti-Alzheimer's molecule.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by learning and memory impairments. Recent studies have suggested that AD can be induced by multiple factors, such as cholinergic system dysfunction and β-amyloid (Aβ) neurotoxicity. It was reported that 6-bromo-N-propionyltryptamine could treat neurological diseases, including AD. In the present study, 6-bromotryptamine A, a derivative of 6-bromo-N-propionyltryptamine, was synthesized by the condensation of 2-(6-bromo-1H-indol-3-yl)ethan-1-amine and 2-(4-bromophenyl)acetic acid, and was used as a potential anti-AD molecule. Furthermore, scopolamine can induce impairments of learning and memory, and was widely used to establish AD animal models. The results demonstrated that 6-bromotryptamine A significantly prevented scopolamine-induced short-term cognitive impairments, as revealed by various behavioral tests in mice. Furthermore, an acetylcholinesterase (AChE) activity assay revealed that 6-bromotryptamine A directly inhibited AChE activity. Notably, it was observed that 6-bromotryptamine A blocked the formation of Aβ oligomer, as evaluated by the dot blot assay. All these results suggested that 6-bromotryptamine A may be used to prevent impairments in short-term learning and memory ability possibly via the inhibition of AChE and the blockade of Aβ oligomer formation.

• Authors: Xiaofeng Jin, Minjun Wang, Jieyi Shentu, Chunhui Huang, Yujing Bai, Hanbo Pan, Difan Zhang, Zhijun Yuan, Hui Zhang, Xiao Xiao, Xiang Wu, Lijian Ding, Qinwen Wang, Shan He, Wei Cui
• Journal: Oncology letters (Oncol Lett) Vol. 19 Issue 2 Pg. 1593-1601 (Feb 2020) ISSN: 1792-1074 [Print] Greece
• PMID: 31966085 (Publication Type: Journal Article)
• Copyright: Copyright © 2020, Spandidos Publications.