Next Article in Journal
Effect of Heat Stress on Yield, Monoterpene Content and Antibacterial Activity of Essential Oils of Mentha x piperita var. Mitcham and Mentha arvensis var. piperascens
Next Article in Special Issue
Structure-Based Drug Design Studies Toward the Discovery of Novel Chalcone Derivatives as Potential Epidermal Growth Factor Receptor (EGFR) Inhibitors
Previous Article in Journal
Structural Revisions in Natural Ellagitannins
Previous Article in Special Issue
The Keap1/Nrf2-ARE Pathway as a Pharmacological Target for Chalcones
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(8), 1902; https://doi.org/10.3390/molecules23081902

Exploiting the Chalcone Scaffold to Develop Multifunctional Agents for Alzheimer’s Disease

1
Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy
2
Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d’Augusto 237, 47921 Rimini, Italy
3
Department of Organic Chemistry and Inorganic Chemistry, School of Sciences, University of Alcalá, E-28871 Alcalá de Henares, Madrid, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 29 May 2018 / Revised: 24 July 2018 / Accepted: 27 July 2018 / Published: 30 July 2018
(This article belongs to the Special Issue Chalcone: A Privileged Structure in Medicinal Chemistry)
Full-Text   |   PDF [8394 KB, uploaded 1 August 2018]   |  

Abstract

Alzheimer’s disease still represents an untreated multifaceted pathology, and drugs able to stop or reverse its progression are urgently needed. In this paper, a series of naturally inspired chalcone-based derivatives was designed as structural simplification of our previously reported benzofuran lead compound, aiming at targeting both acetyl (AChE)- and butyryl (BuChE) cholinesterases that, despite having been studied for years, still deserve considerable attention. In addition, the new compounds could also modulate different pathways involved in disease progression, due to the peculiar trans-α,β-unsaturated ketone in the chalcone framework. All molecules presented in this study were evaluated for cholinesterase inhibition on the human enzymes and for antioxidant and neuroprotective activities on a SH-SY5Y cell line. The results proved that almost all the new compounds were low micromolar inhibitors, showing different selectivity depending on the appended substituent; some of them were also effective antioxidant and neuroprotective agents. In particular, compound 4, endowed with dual AChE/BuChE inhibitory activity, was able to decrease ROS formation and increase GSH levels, resulting in enhanced antioxidant endogenous defense. Moreover, this compound also proved to counteract the neurotoxicity elicited by Aβ1–42 oligomers, showing a promising neuroprotective potential. View Full-Text
Keywords: Alzheimer’s disease; chalcones; cholinesterase inhibitors; antioxidants; neuroprotection Alzheimer’s disease; chalcones; cholinesterase inhibitors; antioxidants; neuroprotection
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).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Rampa, A.; Bartolini, M.; Pruccoli, L.; Naldi, M.; Iriepa, I.; Moraleda, I.; Belluti, F.; Gobbi, S.; Tarozzi, A.; Bisi, A. Exploiting the Chalcone Scaffold to Develop Multifunctional Agents for Alzheimer’s Disease. Molecules 2018, 23, 1902.

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