Multi-Target-Directed Cinnamic Acid Hybrids Targeting Alzheimer's Disease

• Published in: International journal of molecular sciences Vol. 25; no. 1; p. 582
• Main Authors: Drakontaeidi, Aliki, Pontiki, Eleni
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024; MDPI
• Subjects: acetylcholinesterase inhibition; Advertising executives; Alzheimer's disease; Amino acids; antioxidant; Antioxidants; Brain research; Cell cycle; cinnamic acids; Cognition & reasoning; Development and progression; Disease; Drugs; Enzyme kinetics; Health aspects; hybrids; Inflammation; Medical research; multi-target; Oxidative stress; Pathophysiology; Patient compliance; Proteins; Review; Target marketing; antioxidant; Alzheimer’s disease; neuroprotective; acetylcholinesterase inhibition; cinnamic acids; hybrids; multi-target
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25010582

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.