Cited by 225Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsHeterocyclic Compound Synthesis and Bioactivity

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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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Background
Synthesis of Novel Chalcones as Acetylcholinesterase Inhibitors
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Background
Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer’s disease
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Background
Novel Vilazodone–Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation
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Nontoxic and Neuroprotective β-Naphthotacrines for Alzheimer’s Disease
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“However, tacrine was with-drawn from the market due to its adverse effects and hepatotoxicity [251].”
Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors- Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment
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Understanding the conformational flexibility and electrostatic properties of curcumin in the active site of rhAChE via molecular docking, molecular dynamics, and charge density analysis
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“…A (Bai, 2007; Wang et al., 2009), and rivastigmine (Michael et al., 1999) and the synthetic drugs donepezil (Jacobson & Sabbagh, 2008) and tacrine (Tumiatti et al., 2010) are the reported inhibitors of AChE, and are being used for the treatment of AD (Babitha et al., 2014; Murray, Faraoni,…”
Method
Formulation, Characterization and Evaluation against SH-SY5Y Cells of New Tacrine and Tacrine-MAP Loaded with Lipid Nanoparticles
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“In September of 1993, TAC was approved by the FDA for the treatment of Alzheimer’s disease (AD), being the first approved treatment at the time [4,5].”
Method
Design, synthesis and biological assessment of acridine derivatives containing 1,3,4-thiadiazole moiety as novel selective acetylcholinesterase inhibitors
Lotfi, S., Rahmani, T., Hatami, M., Pouramiri, B., Kermani, E. T., Rezvannejad, E., Mortazavi, M., Hafshejani, S. F., Askari, N., Pourjamali, N., et al. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104457 · Cited by 33
Cholinesterase as a Target for Drug Development in Alzheimer’s Disease
Sharma, P. A., Tripathi, M. K., & Shrivastava, S. K. (2019) · Methods in molecular biology · doi:10.1007/978-1-0716-0163-1_18 · Cited by 33

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 (medical) › Cholinesterase and Neurodegenerative Diseases
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Physical Sciences › Chemistry › Organic Chemistry › Heterocyclic Compound Synthesis and Bioactivity
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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