Next Article in Journal
X-ray Crystal Structure, Geometric Isomerism, and Antimicrobial Activity of New Copper(II) Carboxylate Complexes with Imidazole Derivatives
Previous Article in Journal
Dietary Lignans: Definition, Description and Research Trends in Databases Development
Previous Article in Special Issue
Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer’s Disease
Article Menu

Export Article

Open AccessArticle
Molecules 2018, 23(12), 3252; https://doi.org/10.3390/molecules23123252

Multifunctional Donepezil Analogues as Cholinesterase and BACE1 Inhibitors

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Diego Muñoz-Torrero and Michael Decker
Received: 25 October 2018 / Revised: 27 November 2018 / Accepted: 7 December 2018 / Published: 8 December 2018
(This article belongs to the Special Issue Molecules against Alzheimer II)
Full-Text   |   PDF [1802 KB, uploaded 8 December 2018]   |  

Abstract

A series of 22 donepezil analogues were synthesized through alkylation/benzylation and compared to donepezil and its 6-O-desmethyl adduct. All the compounds were found to be potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes responsible for the hydrolysis of the neurotransmitter acetylcholine in Alzheimer’s disease patient brains. Many of them displayed lower inhibitory concentrations of EeAChE (IC50 = 0.016 ± 0.001 µM to 0.23 ± 0.03 µM) and EfBChE (IC50 = 0.11 ± 0.01 µM to 1.3 ± 0.2 µM) than donepezil. One of the better compounds was tested against HsAChE and was found to be even more active than donepezil and inhibited HsAChE better than EeAChE. The analogues with the aromatic substituents were generally more potent than the ones with aliphatic substituents. Five of the analogues also inhibited the action of β-secretase (BACE1) enzyme. View Full-Text
Keywords: Alzheimer’s disease; acetylcholinesterase; butyrylcholinesterase; β-secretase; inhibitors Alzheimer’s disease; acetylcholinesterase; butyrylcholinesterase; β-secretase; inhibitors
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Green, K.D.; Fosso, M.Y.; Garneau-Tsodikova, S. Multifunctional Donepezil Analogues as Cholinesterase and BACE1 Inhibitors. Molecules 2018, 23, 3252.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top