Liu, Wenwu; Liu, Xin; Tian, Liting; Gao, Yaping; Liu, Wenjie; Chen, Huanhua; Jiang, Xiaowen; Xu, Zihua; Ding, Huaiwei; Zhao, Qingchun published an article in 2021. The article was titled 《Design, synthesis and biological evaluation of harmine derivatives as potent GSK-3β/DYRK1A dual inhibitors for the treatment of Alzheimer’s disease》, and you may find the article in European Journal of Medicinal Chemistry.HPLC of Formula: 1692-25-7 The information in the text is summarized as follows:
Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease, characterized by irreversible cognitive impairment, memory loss and behavioral disturbances, ultimately leading to death. Glycogen synthase kinase 3β (GSK-3β) and dual-specificity tyrosine phosphorylation regulated kinase1A (DYRK1A) have gained a lot of attention for its role in tau pathol. To search for potential dual GSK-3β/DYRK1A inhibitors, we focused on harmine, a natural β-carboline alkaloid, which has been extensively studied for its various biol. effects on the prevention of AD. In this study, a new series of harmine derivatives were designed, synthesized and evaluated as dual GSK-3β/DYRK1A inhibitors for their multiple biol. activities. The in vitro results indicated that most of them displayed promising activity against GSK-3β and DYRK1A. Among them, compound ZDWX-25 (I) showed potent inhibitory effects on GSK-3β and DYRK1A with IC50 values of 71 and 103 nM, resp. Mol. modeling and kinetic studies verified that ZDWX-25 could interact with the ATP binding pocket of GSK-3β and DYRK1A. Western blot anal. revealed that ZDWX-25 inhibited hyperphosphorylation of tau protein in okadaic acid (OKA)-induced SH-SY5Y cells. In addition, ZDWX-25 showed good blood-brain barrier penetrability in vitro. More importantly, ZDWX-25 could ameliorate the impaired learning and memory in APP/PS1/Tau transgenic mice. These results indicated that the harmine-based compounds could be served as promising dual-targeted candidates for AD. In the experiment, the researchers used Pyridin-3-ylboronic acid(cas: 1692-25-7HPLC of Formula: 1692-25-7)
Pyridin-3-ylboronic acid(cas: 1692-25-7) belongs to pyridine. Pyridines form stable salts with strong acids. Pyridine itself is often used to neutralize acid formed in a reaction and as a basic solvent. HPLC of Formula: 1692-25-7