Analogues of 2 `-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase
Document Type
Article
Publication Date
1-1-2021
Abstract
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).
Keywords
Alzheimer’, s disease, Acetylcholinesterase, Butyrylcholinesterase, Chalcones, Molecular modelling
Divisions
CHEMISTRY,nanocat,pharchemistry
Funders
Universiti Malaya [PG034-2014A] [RG392-17AFR],Ministry of Education, Malaysia [FRGS FP125-2019A]
Publication Title
Journal of Enzyme Inhibition and Medicinal Chemistry
Volume
36
Issue
1
Publisher
Taylor & Francis Ltd
Publisher Location
2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND