Affiliation:
1. Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Abstract
Progressive cognitive decline in Alzheimer’s disease (AD) is a growing challenge. Present therapies are based on acetylcholinesterase inhibition providing only temporary relief. Promising alternatives include butyrylcholinesterase (BuChE) inhibitors, multi-target ligands (MTDLs) that address the multi-factorial nature of AD, and compounds that target oxidative stress and inflammation. Cinnamate derivatives, known for their neuroprotective properties, show potential when combined with established AD agents, demonstrating improved efficacy. They are being positioned as potential AD therapeutic leads due to their ability to inhibit Aβ accumulation and provide neuroprotection. This article highlights the remarkable potential of cinnamic acid as a basic structure that is easily adaptable and combinable to different active groups in the struggle against Alzheimer’s disease. Compounds with a methoxy substitution at the para-position of cinnamic acid display increased efficacy, whereas electron-withdrawing groups are generally more effective. The effect of the molecular volume is worthy of further investigation.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference131 articles.
1. Alzheimer’s Disease International (2023, December 25). World Alzheimer Report 2019: Attitudes to dementia. London: Alzheimer’s Disease International. Available online: https://www.alzint.org/resource/world-alzheimer-report-2019/.
2. Novel oxoisoaporphine-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation;Tang;Bioorg. Med. Chem. Lett.,2012
3. Alzheimer’s Disease: A General Introduction and Pathomechanism;Finder;J. Alzheimer’s Dis.,2010
4. Phases of Aβ-deposition in the human brain and its relevance for the development of AD;Thal;Neurology,2002
5. Tacrine Derivatives and Alzheimers Disease;Tumiatti;Curr. Med. Chem.,2010