2-Benzyloxynaphthalene Aminoalkylated Chalcone Designed as Acetylcholinesterase Inhibitor: Structural Characterisation, in vitro Biological Activity and Molecular Docking Studies

Aljohani, Ghadah, Ali, Adeeb Al-sheikh, Said, Musa A., Hughes, David L., Alraqa, Shaya Y., Amran, Syazwani, Ahmad, Farediah and Basar, Norazah (2020) 2-Benzyloxynaphthalene Aminoalkylated Chalcone Designed as Acetylcholinesterase Inhibitor: Structural Characterisation, in vitro Biological Activity and Molecular Docking Studies. Journal of Molecular Structure, 1222. ISSN 0022-2860

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Abstract

The design of an acetylcholinesterase inhibitor with multifunctional properties became the perspective for the development of an effective drug against Alzheimer's disease. Towards this target, 1-{4-hydroxy-3-[(piperidin-1-yl)methyl]phenyl}ethan-1-one (chalcone 3) was prepared and studied as an acetylcholinesterase inhibitor. The novel chalcone 3 was synthesised via Claisen-Schmidt condensation reaction with 84% yield and characterized using 1D and 2D NMR spectroscopy. The in vitro bioactivity studies of chalcone 3 demonstrated excellent inhibitory activity against AChE (IC50 1.0 nM) showing 33-fold better inhibition than donepezil, biometal chelating ability and moderate antioxidant activity. Chalcone 3 with these fascinating multifunctional proprieties can be a good candidate for the development of AD treatments. A molecular modelling investigation revealed that chalcone 3 showed dual binding inhibition of AChE enzyme. XRD shows short intra- and inter-molecular interactions with two chalcone 3 molecules per cell. Interesting Hirshfeld Surface Analysis (HSA) was conducted showing explicit agreement with the XRD analysis.

Item Type: Article
Uncontrolled Keywords: acetylcholinesterase (ache),hirshfeld surface analysis,metal chelation,nmr titration, molecular docking,xrd,analytical chemistry,spectroscopy,organic chemistry,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1600/1602
Faculty \ School: Faculty of Science > School of Chemistry
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Depositing User: LivePure Connector
Date Deposited: 22 Jul 2020 02:47
Last Modified: 06 Aug 2020 23:51
URI: https://ueaeprints.uea.ac.uk/id/eprint/76226
DOI: 10.1016/j.molstruc.2020.128898

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