2-Benzyloxynaphthalene aminoalkylated chalcone designed as acetylcholinesterase inhibitor: structural characterisation, in vitro biological activity and molecular docking studies

• Main Authors: Aljohani, G., Ali, A. S., Said, M. A., Hughes, D. L., Alraqa, S. Y., Amran, S., Ahmad, F., Basar, N.
• Format: Article
• Published: Elsevier B.V. 2020
• Subjects: QD Chemistry
• Online Access: http://eprints.utm.my/id/eprint/92899/; http://dx.doi.org/10.1016/j.molstruc.2020.128898

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.