Abstract
Alzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public health. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach is a promising method in search for new drugs for AD. This review updates information on the development of multifunctional potential anti-AD agents published within the last three years. The majority of the recently reported structures are acetylcholinesterase inhibitors, often endowed with some additional properties. These properties enrich the pharmacological profile of the compounds giving hope for not only symptomatic but also causal treatment of the disease. Among these advantageous properties, the most often reported are an amyloid-β antiaggregation activity, inhibition of β-secretase and monoamine oxidase, an antioxidant and metal chelating activity, NOreleasing ability and interaction with cannabinoid, NMDA or histamine H3 receptors. The majority of novel molecules possess heterodimeric structures, able to interact with multiple targets by combining different pharmacophores, original or derived from natural products or existing therapeutics (tacrine, donepezil, galantamine, memantine). Among the described compounds, several seem to be promising drug candidates, while others may serve as a valuable inspiration in the search for new effective therapies for AD.
Keywords: Alzheimer’s disease, antioxidants, β-amyloid anti-aggregation properties, cholinesterase inhibitors, inhibitors of β- secretase, inhibitors of monoamine oxidase A/B, multi-target-directed ligands, neuroprotective properties.
Current Medicinal Chemistry
Title:Recent Development of Multifunctional Agents as Potential Drug Candidates for the Treatment of Alzheimer’s Disease
Volume: 22 Issue: 3
Author(s): Natalia Guzior, Anna Wieckowska, Dawid Panek and Barbara Malawska
Affiliation:
Keywords: Alzheimer’s disease, antioxidants, β-amyloid anti-aggregation properties, cholinesterase inhibitors, inhibitors of β- secretase, inhibitors of monoamine oxidase A/B, multi-target-directed ligands, neuroprotective properties.
Abstract: Alzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public health. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach is a promising method in search for new drugs for AD. This review updates information on the development of multifunctional potential anti-AD agents published within the last three years. The majority of the recently reported structures are acetylcholinesterase inhibitors, often endowed with some additional properties. These properties enrich the pharmacological profile of the compounds giving hope for not only symptomatic but also causal treatment of the disease. Among these advantageous properties, the most often reported are an amyloid-β antiaggregation activity, inhibition of β-secretase and monoamine oxidase, an antioxidant and metal chelating activity, NOreleasing ability and interaction with cannabinoid, NMDA or histamine H3 receptors. The majority of novel molecules possess heterodimeric structures, able to interact with multiple targets by combining different pharmacophores, original or derived from natural products or existing therapeutics (tacrine, donepezil, galantamine, memantine). Among the described compounds, several seem to be promising drug candidates, while others may serve as a valuable inspiration in the search for new effective therapies for AD.
Export Options
About this article
Cite this article as:
Guzior Natalia, Wieckowska Anna, Panek Dawid and Malawska Barbara, Recent Development of Multifunctional Agents as Potential Drug Candidates for the Treatment of Alzheimer’s Disease, Current Medicinal Chemistry 2015; 22 (3) . https://dx.doi.org/10.2174/0929867321666141106122628
DOI https://dx.doi.org/10.2174/0929867321666141106122628 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![](https://cdn.statically.io/img/doi.org/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
B7-H3-targeted Radioimmunotherapy of Human Cancer
Current Medicinal Chemistry Advances in Interleukin-12 Gene Therapy for Acquired Liver Diseases
Current Gene Therapy Cardiovascular Effects of Neuregulin-1/ErbB Signaling: Role in Vascular Signaling and Angiogenesis
Current Pharmaceutical Design Anticancer Mechanisms of Berberine: A Good Choice for Glioblastoma Multiforme Therapy
Current Medicinal Chemistry Advancing Drug Therapy for Brain Tumours: A Current Review of the Pro-inflammatory Peptide Substance P and its Antagonists as Anti-cancer Agents
Recent Patents on CNS Drug Discovery (Discontinued) NPY Signalling Pathway in Bone Homeostasis: Y1 Receptor as a Potential Drug Target
Current Drug Targets Protective Substances Against Zinc-Induced Neuronal Death after Ischemia:Carnosine as a Target for Drug of Vascular Type of Dementia
Recent Patents on CNS Drug Discovery (Discontinued) The Complement Cascade: New Avenues in Stroke Therapy
Current Vascular Pharmacology Recent Advances in Molecular Image-Guided Cancer Radionuclide Therapy
Current Drug Targets Morphine as a Potential Oxidative Stress-Causing Agent
Mini-Reviews in Organic Chemistry Alzheimers Disease and Non-Steroidal Anti-Inflammatory Drugs: Old Therapeutic Tools with Novel Mechanisms of Action?
Current Medicinal Chemistry - Central Nervous System Agents Ginkgo biloba Extract 761: A Review of Basic Studies and Potential Clinical Use in Psychiatric Disorders
CNS & Neurological Disorders - Drug Targets Targeted Hydrolysis of Beta-Amyloid with Engineered Antibody Fragments
Current Alzheimer Research Lipid Nanoparticles for the Delivery of Biopharmaceuticals
Current Pharmaceutical Biotechnology From Antioxidant Chelators to Site-Activated Multi-Target Chelators Targeting Hypoxia Inducing Factor, Beta-Amyloid, Acetylcholinesterase and Monoamine Oxidase A/B
Mini-Reviews in Medicinal Chemistry Bioactive N-Phenylimidazole Derivatives
Current Chemical Biology Small Molecule Toxins Targeting Tumor Receptors
Current Pharmaceutical Design Recent Knowledge on Medicinal Plants as Source of Cholinesterase Inhibitors for the Treatment of Dementia
Mini-Reviews in Medicinal Chemistry Prolyl Oligopeptidase: A Rising Star on the Stage of Neuroinflammation Research
CNS & Neurological Disorders - Drug Targets Targeted Enzyme Prodrug Therapies
Mini-Reviews in Medicinal Chemistry