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Synthesis and evaluation of coumarin/piperazine hybrids as acetylcholinesterase inhibitors

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Abstract

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.

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Acknowledgements

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

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Authors and Affiliations

  1. School of Biological Science and Technology, University of Jinan, Jinan, 250022, China

    Juan Zhang & Cheng-Shi Jiang

  2. Faculty of Ceilandia, University of Brasília, Brasília, 72220275, Brazil

    Juan Zhang

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  1. Juan Zhang
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  2. Cheng-Shi Jiang
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Correspondence to Cheng-Shi Jiang.

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Zhang, J., Jiang, CS. Synthesis and evaluation of coumarin/piperazine hybrids as acetylcholinesterase inhibitors. Med Chem Res 27, 1717–1727 (2018). https://doi.org/10.1007/s00044-018-2185-x

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  • DOI: https://doi.org/10.1007/s00044-018-2185-x

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