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

Publication Title

Journal of Enzyme Inhibition and Medicinal Chemistry

Divisions

CHEMISTRY,nanocat,pharchemistry

Funders

Universiti Malaya [PG034-2014A] [RG392-17AFR],Ministry of Education, Malaysia [FRGS FP125-2019A]

Volume

36

Issue

1

Publisher

Taylor & Francis Ltd

Publisher Location

2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND

This document is currently not available here.

Share

COinS