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
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
Oligomeric Amyloid β -Protein as a Therapeutic Target in Alzheimers Disease: Its Significance Based on its Distinct Localization and the Occurrence of a Familial Variant Form
Current Alzheimer Research Blood Pressure and Cognitive Impairment in the Elderly
Current Hypertension Reviews Fructose 1,6-Bisphosphate: A Summary of Its Cytoprotective Mechanism
Current Medicinal Chemistry The Glutamatergic Hypothesis for Down Syndrome: The Potential Use of N-Methyl-D-Aspartate Receptor Antagonists to Enhance Cognition and Decelerate Neurodegeneration
CNS & Neurological Disorders - Drug Targets CD14-Dependent Innate Immunity-Mediated Neuronal Damage in Vivo is Suppressed by NSAIDs and Ablation of a Prostaglandin E2 Receptor, EP2
Current Medicinal Chemistry - Central Nervous System Agents Cardiovascular Risk in Patients with Primary Hyperparathyroidism
Current Pharmaceutical Design Drosophila melanogaster in the Study of Human Neurodegeneration
CNS & Neurological Disorders - Drug Targets Solution NMR Studies of Aβ Monomer Dynamics
Protein & Peptide Letters A Nanotechnological Approach to the Management of Alzheimer Disease and Type 2 Diabetes
CNS & Neurological Disorders - Drug Targets Applying Knowledge of Enzyme Biochemistry to the Prediction of Functional Sites for Aiding Drug Discovery
Current Topics in Medicinal Chemistry Neuroinflammation and Complexes of 17β -Hydroxysteroid Dehydrogenase type 10 - Amyloid β in Alzheimer's Disease
Current Alzheimer Research Global View on Alzheimer’s Disease and Diabetes Mellitus: Threats, Risks and Treatment Alzheimer’s Disease and Diabetes Mellitus
Current Alzheimer Research Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) PSEN1 Promoter Demethylation in Hyperhomocysteinemic TgCRND8 Mice is the Culprit, not the Consequence
Current Alzheimer Research Opinion Paper: A Cognitive-cultural Segregation and the Three Stages of Aging
Current Aging Science Second-Generation Antipsychotic Agents: A Review of Safety Profiles
Current Psychiatry Reviews Substance Abuse and Movement Disorders
Current Drug Abuse Reviews Medical Treatment of Peripheral Arterial Disease: Current Concepts and Future Options
Vascular Disease Prevention (Discontinued) Xuesaitong May Protect Against Ischemic Stroke by Modulating Microglial Phenotypes and Inhibiting Neuronal Cell Apoptosis via the STAT3 Signaling Pathway
CNS & Neurological Disorders - Drug Targets Connected Speech Deficit as an Early Hallmark of CSF-defined Alzheimer’s Disease and Correlation with Cerebral Hypoperfusion Pattern
Current Alzheimer Research