E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Cholinesterase Inhibitors"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 31 August 2019

Special Issue Editor

Guest Editor
Dr. Ludovic Jean

University Rouen Normandie, Laboratory COBRA UMR CNRS 6014, 76000 Rouen, France
Website | E-Mail
Interests: cholinesterase inhibitors; cholinesterase reactivators; multi-target anti-Alzheimer agents

Special Issue Information

Dear Colleagues,

Acetylcholinesterase (AChE, EC 3.1.1.7) plays a pivotal role in cholinergic transmission in the central nervous system and at the neuromuscular junctions (NMJ). Even if its physiological role has not yet been identified, butyrylcholinesterase (BChE, EC 3.1.1.8), also named pseudocholinesterase, is well known to play a role in metabolizing bioactive esters (e.g., succinylcholine, cocaine). The effects of cholinesterase inhibitors (ChEIs) have been investigated in diseases associated with a cholinergic deficit, such as Alzheimer's disease (AD) and other dementias. Although ChEIs afford mostly a symptomatic response to AD patients, the development of new ChEIs (e.g., multifunctional ligands, selective BChE inhibitors) remains of interest to treat neurodegenerative diseases. ChEIs may also be used as a treatment for an autoimmune disease named Myastenia Gravis, by targeting nicotinic acetylcholine receptors at the NMJ, and as a prophylactic treatment against organophosphorus nerve agents poisoning. On the basis of their mechanism of action, ChEIs are classified into three groups: reversible (e.g., tacrine); pseudoirreversible (e.g., rivastigmine), and irreversible (e.g., echothiophate).

In this Special Issue, we invite you to submit original research papers or reviews, which report on the design, synthesis, and biological evaluation of novel ChEIs.

Dr. Ludovic Jean
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Dementia
  • Myasthenia Gravis
  • Organophosphorus compounds
  • Drug discovery
  • Rational design

Published Papers (2 papers)

View options order results:
result details:
Displaying articles 1-2
Export citation of selected articles as:

Research

Open AccessFeature PaperArticle
QuinoxalineTacrine QT78, a Cholinesterase Inhibitor as a Potential Ligand for Alzheimer’s Disease Therapy
Molecules 2019, 24(8), 1503; https://doi.org/10.3390/molecules24081503
Received: 19 February 2019 / Revised: 14 April 2019 / Accepted: 15 April 2019 / Published: 17 April 2019
PDF Full-text (3390 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 [...] Read more.
We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 μM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 ± 1.3 μM; IC50 (hBuChE) = 6.79 ± 0.33 μM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer’s disease. Full article
(This article belongs to the Special Issue Cholinesterase Inhibitors)
Figures

Figure 1

Open AccessFeature PaperArticle
Design, Synthesis, and In Vitro Biological Activities of a Bio-Oxidizable Prodrug to Deliver Both ChEs and DYRK1A Inhibitors for AD Therapy
Molecules 2019, 24(7), 1264; https://doi.org/10.3390/molecules24071264
Received: 4 March 2019 / Revised: 27 March 2019 / Accepted: 28 March 2019 / Published: 1 April 2019
PDF Full-text (1584 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Despite their side effects, cholinesterase (ChE) inhibitors remain the only approved drugs to treat Alzheimer’s disease patients, along with the N-methyl-d-aspartate (NMDA) receptor antagonist memantine. In the last few years, the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has also been [...] Read more.
Despite their side effects, cholinesterase (ChE) inhibitors remain the only approved drugs to treat Alzheimer’s disease patients, along with the N-methyl-d-aspartate (NMDA) receptor antagonist memantine. In the last few years, the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has also been studied as a promising target for the development of new drugs for this pathology. In this context, and based on our previous characterization of bio-oxidizable prodrugs of potent acetylcholinesterase (AChE) inhibitors, we envisioned a strategy involving the synthesis of a bio-oxidizable prodrug of both ChE and DYRK1A inhibitors. To this end, we fixed our interest on a known potent inhibitor of DYRK1A, namely INDY. The designed prodrug of both ChE and DYRK1A inhibitors was successfully synthesized, connecting both inhibitors by a carbonate link. This prodrug and its corresponding drug were then evaluated as ChEs and DYRK1A inhibitors. Remarkably, in vitro results were in accordance with the starting hypothesis, showing a relative inactivity of the prodrug against DYRK1A and ChEs and a potent inhibition of ChEs by the oxidized form. Molecular docking and kinetic studies of ChE inhibition by the active compound are also discussed in this report. Full article
(This article belongs to the Special Issue Cholinesterase Inhibitors)
Figures

Graphical abstract

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