Synthesis and Biological Evaluation of Thiazole-Based Derivatives as Potential Acetylcholinesterase Inhibitors

Aya Y Hemaida; Ghada S Hassan; Azza R Maarouf; Jacques Joubert; Ali A El-Emam

doi:10.1021/acsomega.1c02549

Synthesis and Biological Evaluation of Thiazole-Based Derivatives as Potential Acetylcholinesterase Inhibitors

ACS Omega. 2021 Jul 19;6(29):19202-19211. doi: 10.1021/acsomega.1c02549. eCollection 2021 Jul 27.

Authors

Aya Y Hemaida¹, Ghada S Hassan¹, Azza R Maarouf¹, Jacques Joubert², Ali A El-Emam¹

Affiliations

¹ Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
² Pharmaceutical Chemistry, School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa.

Abstract

Nineteen new thiazole-based derivatives were synthesized and their structures characterized with analytical and spectral data. The in vitro assessment of their acetylcholinesterase (AChE) inhibitory activity revealed that compounds 10 and 16 produced potent AChE inhibitory activities with IC₅₀ values of 103.24 and 108.94 nM, respectively. Compounds 13, 17, 18, 21, 23, 31, and 33 displayed moderate activity with 25-50% relative potency compared to the known potent AChE inhibitor donepezil. Molecular docking studies of the active compounds docked within the active site cavity of AChE showed a binding orientation similar to that of donepezil, with good predicted binding affinities. These compounds could therefore be considered as potential lead compounds for the development of new and potentially improved AChE inhibitors.