Abstract
Alzheimer’s disease (AD) is the most prevalent form of dementia and affects approximately 24 million people worldwide. One possible approach for the treatment of this disease is the restoration of the level of acetylcholine (ACh) through the inhibition of acetylcholinesterase (AChE) with reversible inhibitors. Naturally occurring alkaloids are an important source of AChE inhibitors. Galantamine and huperzine A have been used for the clinical treatment of AD patients. In this review, we summarise the natural products and their derivatives that were reported to act as AChE inhibitors for the treatment of AD in 2010-2013. Several characteristics were summarised from the literature results: 1) Amongst all of the natural products with AChE inhibitory activity, alkaloids appear to be the most promising compound class. 2) Coumarins, flavonoids, stilbenes, and other natural products are also important AChE inhibitors from natural products. Among these inhibitors, 146 (IC50 = 0.573 µM) was identified as the most potent AChE inhibitor. 3) A coumarin derivative (117, IC50 = 0.11 nM) exhibited more than 100-fold superior activity compared with the reference drug donepezil hydrochloride (IC50 = 14 nM). In conclusion, natural products and their derivatives are promising leads for the development of new drugs for the future treatment of AD.
Keywords: Acetylcholinesterase inhibitors, Alzheimer’s disease, Alkaloids, Coumarins, Docking study, Flavonoids, Natural products, Structure-activity relationship.
Current Topics in Medicinal Chemistry
Title:Natural Products as Sources of New Lead Compounds for the Treatment of Alzheimer’s Disease
Volume: 13 Issue: 15
Author(s): Ling Huang, Tao Su and Xingshu Li
Affiliation:
Keywords: Acetylcholinesterase inhibitors, Alzheimer’s disease, Alkaloids, Coumarins, Docking study, Flavonoids, Natural products, Structure-activity relationship.
Abstract: Alzheimer’s disease (AD) is the most prevalent form of dementia and affects approximately 24 million people worldwide. One possible approach for the treatment of this disease is the restoration of the level of acetylcholine (ACh) through the inhibition of acetylcholinesterase (AChE) with reversible inhibitors. Naturally occurring alkaloids are an important source of AChE inhibitors. Galantamine and huperzine A have been used for the clinical treatment of AD patients. In this review, we summarise the natural products and their derivatives that were reported to act as AChE inhibitors for the treatment of AD in 2010-2013. Several characteristics were summarised from the literature results: 1) Amongst all of the natural products with AChE inhibitory activity, alkaloids appear to be the most promising compound class. 2) Coumarins, flavonoids, stilbenes, and other natural products are also important AChE inhibitors from natural products. Among these inhibitors, 146 (IC50 = 0.573 µM) was identified as the most potent AChE inhibitor. 3) A coumarin derivative (117, IC50 = 0.11 nM) exhibited more than 100-fold superior activity compared with the reference drug donepezil hydrochloride (IC50 = 14 nM). In conclusion, natural products and their derivatives are promising leads for the development of new drugs for the future treatment of AD.
Export Options
About this article
Cite this article as:
Huang Ling, Su Tao and Li Xingshu, Natural Products as Sources of New Lead Compounds for the Treatment of Alzheimer’s Disease, Current Topics in Medicinal Chemistry 2013; 13 (15) . https://dx.doi.org/10.2174/15680266113139990142
DOI https://dx.doi.org/10.2174/15680266113139990142 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- 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
-
Beneficial Actions of Polyunsaturated Fatty Acids in Cardiovascular Diseases: But, How and Why?
Current Nutrition & Food Science Insulin Resistance and Alzheimers Disease Pathogenesis: Potential Mechanisms and Implications for Treatment
Current Alzheimer Research Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) Targeting the Role of Astrocytes in the Progression of Alzheimers Disease
Current Signal Transduction Therapy Hybrid PET Imaging in Neurologic Disease: PET/MRI Rather than PET/CT
Current Medical Imaging Effect of HAART on Salivary Composition and Oxidative Profile in HIVInfected Patients
Current HIV Research Immunophilins in Nervous System Degeneration and Regeneration
Current Topics in Medicinal Chemistry Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?
Current Pharmaceutical Design Novel Therapeutic Strategies for Dementia
CNS & Neurological Disorders - Drug Targets Biochemical Markers and Risk Factors of Alzheimers Disease
Current Alzheimer Research Exploring the Role of Gene Therapy for Neurological Disorders
Current Gene Therapy Neuroprotective Efficacy of the Peroxisome Proliferator-Activated Receptor-γ Ligand in Chronic Cerebral Hypoperfusion
Current Neurovascular Research Antiplatelet Treatment in Ischemic Stroke Treatment
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: Psychogeriatrics: An Interdisciplinary Approach)
Current Psychopharmacology Molecular Docking Study of a Series of Substituted Xanthone Derivatives as Novel COX-2 Inhibitors Targeting Prostaglandin Endoperoxide Synthase -2
Current Enzyme Inhibition Neurotransmitter Regulation of Adult Neurogenesis: Putative Therapeutic Targets
CNS & Neurological Disorders - Drug Targets Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease
Current Medicinal Chemistry Development of Polymeric Nanocarriers for Brain Targeted Delivery of Atorvastatin: A Quality-By-Design Approach
Drug Delivery Letters Glycemic Control is Related to Cognitive Dysfunction in Elderly People with Type 2 Diabetes Mellitus in a Rural Chinese Population
Current Alzheimer Research NMDA Receptor Antagonists: Repositioning of Memantine as a Multitargeting Agent for Alzheimer's Therapy
Current Pharmaceutical Design