In-silico docking of curcumin derivatives against amyloid beta
Journal name: World Journal of Pharmaceutical Research
Original article title: In-silico docking of curcumin and its derivatives against amyloid beta peptide in alzheimer’s disease
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Kumar Gaurav, Richa Srivastava, and Saurabh Virdi
World Journal of Pharmaceutical Research:
(An ISO 9001:2015 Certified International Journal)
Full text available for: In-silico docking of curcumin and its derivatives against amyloid beta peptide in alzheimer’s disease
Source type: An International Peer Reviewed Journal for Pharmaceutical and Medical and Scientific Research
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Summary of article contents:
Introduction
Alzheimer's disease (AD) is a neurodegenerative condition characterized by the accumulation of amyloid beta peptide (Aβ) and neurofibrillary tangles leading to cognitive decline and ultimately death. Current treatments primarily focus on increasing acetylcholine levels in the brain via cholinesterase inhibitors, yet they do not address the underlying cause of amyloid aggregation. In light of these limitations, researchers are exploring alternative treatment options using natural compounds such as curcumin, which is derived from turmeric. This study investigates the potential of curcumin and its derivatives to inhibit Aβ aggregation using in-silico molecular docking methods.
The Role of Amyloid Beta Peptide
Amyloid beta peptide is a crucial player in the pathogenesis of Alzheimer’s disease, with its aggregation forming toxic plaques in the brain. The peptide originates from the proteolytic cleavage of amyloid precursor protein (APP) and exists in various forms, with Aβ40 and Aβ42 being the most abundant. The aggregation process involves the formation of oligomers, which are believed to be cytotoxic and contribute to neuronal damage. Several hypotheses, including the amyloid hypothesis, highlight the importance of controlling Aβ aggregation as a viable therapeutic strategy for combating AD. Interventions targeting amyloidogenic processes, such as inhibition of assembly or breakdown of existing aggregates, are critical for potential therapeutic advances.
Curcumin's Antioxidant and Anti-Aggregation Properties
Curcumin, a natural polyphenol from turmeric, has been recognized for its numerous therapeutic effects, including its antioxidant, anti-inflammatory, and antimicrobial properties. More specifically, curcumin has demonstrated the ability to inhibit Aβ aggregation and interfere with oligomerization more effectively than some conventional nonsteroidal anti-inflammatory drugs (NSAIDs). This study posits that curcumin's ability to chelate metals, which are implicated in AD, may further contribute to its neuroprotective effects, thereby presenting a promising natural alternative for AD treatment.
Molecular Docking Studies
The study employed molecular docking techniques to assess the binding affinities of curcumin and its derivatives against the Aβ peptide. The derivatives were systematically evaluated using various parameters such as binding energy and inhibition constant, with curcumin derivatives demonstrating varying degrees of interaction with key amyloidogenic regions in the peptide. Notably, CurL6 emerged as the most promising candidate, exhibiting the highest binding affinity and lowest inhibition constant. Such computational approaches provide valuable insights into the drug-like properties of curcumin derivatives, paving the way for their potential development as treatment options for AD.
Conclusion
The investigation underscores the significant potential of curcumin and its derivatives in targeting and inhibiting amyloid beta peptide aggregation, a pivotal factor in Alzheimer's disease progression. While CurL6 appears to be the most effective candidate based on binding affinity metrics, further research, including in vivo studies and clinical trials, is essential to validate the therapeutic efficacy of these compounds. In the realm of drug discovery for AD, leveraging computational methods alongside biochemical evaluation offers a promising pathway for developing effective treatments to mitigate this devastating disease.
FAQ section (important questions/answers):
What is the primary cause of Alzheimer's disease according to the study?
Alzheimer's disease is primarily caused by the accumulation of aggregated beta amyloid peptide (Aβ) in the brain, which leads to neurotoxicity and contributes to the progressive loss of synapses and neurons.
What role does curcumin play in Alzheimer's disease treatment?
Curcumin is a natural polyphenol derived from turmeric that exhibits various therapeutic effects, including the potential to inhibit amyloid beta aggregation and prevent the formation of cytotoxic aggregates associated with Alzheimer’s disease.
How does molecular docking help in drug discovery?
Molecular docking is a computational method used to study binding affinities and predict the activity of drug candidates. It aids in identifying potential drug compounds by simulating interactions between ligands and target proteins.
Which curcumin derivative showed the best docking results?
The curcumin derivative CurL6 demonstrated the best docking results with a binding energy of -3.26 kcal/mol and an inhibition constant of 4.10 mM, making it a promising candidate for Alzheimer's treatment.
What parameters were assessed during the docking simulations?
The simulations assessed parameters such as binding energy, inhibition constant, intermolecular energy, and hydrogen bond interactions to evaluate the effectiveness of curcumin and its derivatives against amyloid beta peptide.
What further studies are suggested for curcumin derivatives?
Future investigations should include in vivo studies, clinical trials, and further analysis of biochemical interactions involving compounds like tau protein to validate the therapeutic potential of curcumin derivatives in Alzheimer’s disease.
Glossary definitions and references:
Scientific and Ayurvedic Glossary list for “In-silico docking of curcumin derivatives against amyloid beta”. This list explains important keywords that occur in this article and links it to the glossary for a better understanding of that concept in the context of Ayurveda and other topics.
1) Beta (Bēṭa, Beṭa):
Beta refers to the amyloid beta peptide (Aβ), a crucial component in Alzheimer's disease pathogenesis. Its accumulation in the brain is a hallmark of the disease, leading to neurotoxicity and cognitive decline. Understanding its structure and interactions is vital for developing therapeutics aimed at preventing its aggregation.
2) Drug:
Drugs are substances used to diagnose, treat, or prevent diseases. In the context of Alzheimer's disease, drug discovery focuses on compounds that inhibit amyloid beta aggregation, aiming to alleviate symptoms or halt neurodegeneration. The study explores the potential of curcumin derivatives as novel drugs.
3) Disease:
A disease is a pathological condition characterized by symptoms and dysfunction. Alzheimer's disease is a progressive neurodegenerative disease that leads to cognitive decline and memory loss. The text explores molecular mechanisms underlying this condition, emphasizing the need for effective treatments to combat its progression.
4) Kumar (Kumār):
Kumar refers to Dr. Kumar Gaurav, the lead author of the study on curcumin and amyloid beta peptide interactions. His research aims to explore the potential therapeutic effects of curcumin derivatives on Alzheimer's disease, contributing valuable insights into drug discovery for neurodegenerative disorders.
5) Table:
A table in research articles summarizes data, facilitating comparison and analysis. In this study, a table presents docking scores, binding energies, and inhibition constants of curcumin and its derivatives against amyloid beta peptide, aiding in the identification of promising candidates for Alzheimer's treatment.
6) Calculation:
Calculations in this study refer to the computational evaluations performed during molecular docking simulations. Accurate calculations of binding energies, inhibition constants, and intermolecular energies are crucial for understanding how curcumin and its derivatives interact with amyloid beta peptide, guiding potential therapeutic approaches.
7) Delhi:
Delhi is the capital city of India and the location of the research conducted by the authors affiliated with Delhi Technological University. The regional context highlights the growing interest in traditional medicine and natural compounds, such as curcumin, for addressing prevalent health issues like Alzheimer's disease.
8) Study (Studying):
A study encompasses research efforts aimed at investigating hypotheses and generating new knowledge. This particular study focuses on in-silico docking of curcumin derivatives to amyloid beta peptide, analyzing their potential efficacy in treating Alzheimer’s disease by preventing peptide aggregation and toxicity.
9) Accumulation (Accumulating, Accumulate):
Accumulation refers to the buildup of substances over time. In Alzheimer's disease, the accumulation of amyloid beta peptide in the brain is critical, as it forms plaques that disrupt neuron function and lead to cognitive decline. Understanding this process is essential for developing effective interventions.
10) Species:
Species in this context relates to the types of compounds being studied; specifically, different curcumin derivatives examined for their potential to interact with amyloid beta peptide. Each derivative's unique structural properties can influence its efficacy as a therapeutic agent against Alzheimer’s disease.
11) India:
India is the country where the research was conducted, specifically at Delhi Technological University. The country's rich tradition of using natural products, like turmeric and curcumin, in medicine underscores the relevance of exploring these compounds for modern therapeutic applications, particularly in neurodegenerative diseases.
12) Turmeric:
Turmeric is a spice commonly used in Asian cuisine and traditional medicine. Its active compound, curcumin, has garnered attention for its potential neuroprotective effects. This study investigates turmeric-derived curcumin’s ability to inhibit amyloid beta aggregation, offering insights into alternative therapeutic strategies for Alzheimer's disease.
13) Activity:
Activity in this research refers to the biological effects of curcumin and its derivatives on amyloid beta peptide interactions. The study evaluates how these compounds can inhibit aggregation and neurotoxicity, thereby potentially improving cognitive functions in Alzheimer's disease patients through these activities.
14) Death:
Death in the context of Alzheimer’s disease refers to the eventual progression of this debilitating condition that ultimately leads to mortality. Understanding the disease's mechanisms, including amyloid beta accumulation, is crucial for developing effective treatments that could prolong life and enhance the quality of life.
15) Discussion:
The discussion section in research papers interprets the findings and contextualizes them within existing literature. Here, the results of docking studies on curcumin and its derivatives are analyzed, fostering a dialogue on their therapeutic potential against Alzheimer’s disease and paving the way for future research.
16) Srivastava (Sri-vastava, Shrivastava, Shri-vastava):
Srivastava refers to one of the co-authors, Richa Srivastava, involved in the research study. Her contributions to the study's design and implementation help ensure thorough exploration of curcumin’s derivatives in relation to Alzheimer's disease, underscoring collaborative efforts in scientific research.
17) Toxicity:
Toxicity is the degree to which a substance can cause harm to an organism. In Alzheimer's research, minimizing toxicity is essential when developing new therapeutic agents. Curcumin is noted for its low toxicity profile, making it a candidate for safer treatment options compared to conventional drugs.
18) Nature:
Nature in this context emphasizes the natural origin of curcumin, derived from turmeric. The study explores the potential of natural compounds as therapeutic agents for Alzheimer's disease, highlighting a shift towards integrating traditional medicine with modern therapeutic strategies in addressing health challenges.
19) Powder:
Powder refers to the form of curcumin extracted from turmeric rhizomes. This formulation is crucial in the study, as it underlines the bioactive nature of curcumin and its derivatives, facilitating their evaluation in molecular docking studies aimed at therapeutic applications against amyloid beta accumulation.
20) Diet:
Diet pertains to the consumption of foods, including those rich in curcumin like turmeric. The study acknowledges the role of dietary components in potentially mitigating Alzheimer's disease risk, suggesting that incorporating curcumin-rich foods could have a positive effect on brain health and amyloid peptide interactions.
21) Gold (Golden):
Gold refers to the various molecular docking software utilized in the study, such as GOLD (Genetic Optimisation for Ligand Docking). These tools provide advanced algorithms for predicting molecular interactions and affinities, critical for identifying lead compounds in the quest for effective Alzheimer’s treatments.
Other Science Concepts:
Discover the significance of concepts within the article: ‘In-silico docking of curcumin derivatives against amyloid beta’. Further sources in the context of Science might help you critically compare this page with similair documents:
Alzheimer's disease, Oxidative stress, Molecular docking, Curcumin, Synthetic drugs.