Medicinal Chemistry Research

, Volume 27, Issue 6, pp 1717–1727 | Cite as

Synthesis and evaluation of coumarin/piperazine hybrids as acetylcholinesterase inhibitors

  • Juan Zhang
  • Cheng-Shi Jiang
Original Research


A series of new coumarin/piperazine hybrids were synthesized and evaluated for anticholinesterase activity. Among them, compounds 4d and 4t exhibited potent human acetylcholinesterase (hAChE) inhibitory activity with IC50 values of 2.42 and 9.89 μM, respectively, and 4t displayed highest selectivity toward hAChE over human butyrylcholinesterase (hBChE) by 9.8-fold. In addition, both compounds did not show observed cytotoxicity against SH-SY5Y neuroblastoma cell line at 100 μM. Kinetic analysis in tandem with molecular docking study revealed that these hybrids targeted both catalytic active site (CAS) and peripheral anionic site (PAS) of hAChE. The preliminary results highlighted 4t as an anti-Alzheimer’s disease lead compound worthy of further investigation.


Coumarin/piperazine hybrid Acetylcholinesterase inhibitor Molecular docking Cytotoxicity Alzheimer’s disease 



This research work was financially supported by the Natural Science Foundation of China (No. 21672082) and Shandong Key Development Project (No. 2016GSF201209).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2185_MOESM1_ESM.docx (3.4 mb)
Supplementary Information


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Biological Science and TechnologyUniversity of JinanJinanChina
  2. 2.Faculty of CeilandiaUniversity of BrasíliaBrasíliaBrazil

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