Journal of Enzyme Inhibition and Medicinal Chemistry (Dec 2023)

Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer’s disease

  • Hongsong Chen,
  • Jing Mi,
  • Sen Li,
  • Zhengwei Liu,
  • Jing Yang,
  • Rui Chen,
  • Yujie Wang,
  • Yujuan Ban,
  • Yi Zhou,
  • Wu Dong,
  • Zhipei Sang

DOI
https://doi.org/10.1080/14756366.2023.2169682
Journal volume & issue
Vol. 38, no. 1

Abstract

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A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer’s disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1β and NO. In addition, compound 3f presented significant neuroprotective effect on Aβ25-35-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl3-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.

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