Journal of Hebei University(Natural Science Edition) >

2024 , Vol. 44 >Issue 4: 382 - 389

DOI: https://doi.org/10.3969/j.issn.1000-1565.2024.04.006

Design and synthesis of quinoline-triazine derivatives and in vitro butyrylcholinesterase inhibitory activity

  • DONG Change ,
  • LI Rui ,
  • XUE Xuanyi ,
  • ZHANG Zhaoyuan ,
  • SHI Dahua
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  • 1. School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China; 2. Jiangsu Henghai Pharmaceutical Research Institute Co., LTD, Lianyungang 222005, China

Received date: 2023-04-27

  Online published: 2024-07-12

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Abstract

Using 2-(chloromethyl)quinoline hydrochloride as raw material, quinoline-triazine derivatives(5a-5f)with novel structures were obtained by oxidation and nucleophilic substitution reaction. The structure and design of all compounds were confirmed to be consistent using characterization methods such as IR, 1H NMR, 13C NMR, and HRMS. Ellman method was used to test the activity of the target compounds against butyrylcholinesterase in vitro. The results showed that all compounds inhibition rate were more than 50% at 80 μmol/L. Compound 5e［IC50=(1.71±0.04)μmol/L］ had the best activity and was stronger than the positive control donepezil ［IC50=(12.69±0.07)μmol/L］. Further studies on the molecular docking of 5e and BuChE showed that the quinoline ring and sulfur atom in the structure could interact with the residues Ser198, His438, Trp82 and Thr120 of the enzyme active site through hydrogen bonding. Thus, compound 5e is the most active structure screened in this study, which provides a new structural direction for Alzheimers disease(AD)research and is of significance for further research.

Key words： quinoline; 1,2,4-triazine derivatives; butyrylcholinesterase inhibitors; Alzheimers disease

Cite this article

DONG Change , LI Rui , XUE Xuanyi , ZHANG Zhaoyuan , SHI Dahua . Design and synthesis of quinoline-triazine derivatives and in vitro butyrylcholinesterase inhibitory activity[J]. Journal of Hebei University(Natural Science Edition), 2024 , 44(4) : 382 -389 . DOI: 10.3969/j.issn.1000-1565.2024.04.006

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