Tacrine Derivatives and Alzheimers Disease

Tumiatti, V.; Minarini, A.; Bolognesi, M.L.; Milelli, A.; Rosini, M.; Melchiorre, C.

doi:10.2174/092986710791111206

Cited by 225Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsSynthesis and biological activity

Tacrine Derivatives and Alzheimers Disease

Tumiatti, V., Minarini, A., Bolognesi, M.L., Milelli, A., Rosini, M., Melchiorre, C.·2010·Current Medicinal Chemistry

DOI 10.2174/092986710791111206

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Abstract

To date, the pharmacotherapy of Alzheimer's disease (AD) has relied on acetylcholinesterase (AChE) inhibitors (AChEIs) and, more recently, an N-methyl-D-aspartate receptor (NMDAR) antagonist. AD is a multifactorial syndrome with several target proteins contributing to its etiology. "Multi-target-directed ligands" (MTDLs) have great potential for treating complex diseases such as AD because they can interact with multiple targets. The design of compounds that can hit more than one specific AD target thus represents an innovative strategy for AD treatment. Tacrine was the first AChEI introduced in therapy. Recent studies have demonstrated its ability to interact with different AD targets. Furthermore, numerous tacrine homo- and heterodimers have been developed with the aim of improving and enlarging its biological profile beyond its ability to act as an AChEI. Several tacrine hybrid derivatives have been designed and synthesized with the same goal. This review will focus on and summarize the last two years of research into the development of tacrine derivatives able to hit AD targets beyond simple AChE inhibition.

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Tacrine has been widely exploited as a starting fragment of hybrids able to combine AChE inhibition with other additional effects and reduced hepatotoxicity, thanks to its low molecular weight and high synthetic accessibility.
“In spite of that, thanks to its low-molecular weight and high synthetic accessibility, 16 has been widely exploited as a starting fragment of hybrids able to combine AChE inhibition with other additional effects and endowed with reduced hepatotoxicity.91”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [91]

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Method
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Authors: Tumiatti, V., Minarini, A., Bolognesi, M. L., Milelli, A., Rosini, M., & Melchiorre, C.
Affiliations: University of Bologna (IT)
Corresponding author: Rosini, M.
Melchiorre, C.
ORCID: Tumiatti, V.
Minarini, A.
Bolognesi, M.L.
Milelli, A.
Rosini, M.
Venue: Current Medicinal Chemistry
Publisher: Bentham Science Publishers Ltd.
Published: 2010-06-01
Volume: 17
Issue: 17
Pages: 1825-1838
ISSN: 0929-8673 (ISSN-L)
DOI: 10.2174/092986710791111206
OpenAlex: W2121322934
Cited by: 225
References: 0
Citations by year: 2026: 9 · 2025: 8 · 2024: 8 · 2023: 4 · 2022: 18 · 2021: 14 · 2020: 13 · 2019: 28 · 2018: 12 · 2017: 22 · 2016: 19 · 2015: 16 · 2014: 17 · 2013: 14 · 2012: 12
FWCI: 9.92
Type: journal article
Language: en
Open access: closed
Locations: Current Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords: tacrine derivatives, Alzheimer's disease, acetylcholinesterase inhibitors, multi-target-directed ligands, NMDA receptor antagonists, drug repurposing
MeSH terms: Acetylcholinesterase, Alzheimer Disease, Cholinesterase Inhibitors, Humans, Models, Molecular, Structure-Activity Relationship, Tacrine, Amyloid beta-Peptides

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Tacrine Derivatives and Alzheimers Disease

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