Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase

Sukumaran, Sri Devi and Nasir, Shah Bakhtiar and Tee, Jia Ti and Buckle, Michael J. C. and Othman, Rozana and Abd Rahman, Noorsaadah and Lee, Vannajan Sanghiran and Bukhari, Syed Nasir Abbas and Chee, Chin Fei (2021) Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase. Journal of Enzyme Inhibition and Medicinal Chemistry, 36 (1). pp. 130-137. DOI

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A series of C4-substituted tertiary nitrogen-bearing 2 `-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2 `-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound 4c was identified as the most potent AChE inhibitor (IC50: 3.3 mu M) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound 4c interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound 4c based on its blood-brain barrier penetrating. Overall, the results suggest that this 2 `-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer's disease (AD).

Item Type: Article
Funders: Universiti Malaya [PG034-2014A] [RG392-17AFR], Ministry of Education, Malaysia [FRGS FP125-2019A]
Uncontrolled Keywords: Alzheimer’ s disease; Acetylcholinesterase; Butyrylcholinesterase; Chalcones; Molecular modelling
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science > Department of Chemistry
Nanotechnology & Catalysis Research Centre
Faculty of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User: Ms Zaharah Ramly
Date Deposited: 13 Jun 2022 02:04
Last Modified: 13 Jun 2022 02:04

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