Machine Learning, Molecular Modeling and Qsar Studies of Natural Products against Alzheimer’s Disease

2021 ◽  
Vol 28 ◽  
Author(s):  
Érika Paiva de Moura ◽  
Natan Dias Fernandes ◽  
Alex France Messias Monteiro ◽  
Herbert Igor Rodrigues de Medeiros ◽  
Marcus Tullius Scotti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Neurodegenerative Disorder ◽  
Quantitative Structure Activity Relationship ◽  
World Health ◽  
Qsar Studies ◽  
Structure Activity ◽  
Gradual Loss ◽  
Health Organization

Background: Alzheimer's disease (AD) is a very common neurodegenerative disorder in individuals over 65 years of age, however, younger individuals can also be affected due to early brain damage. Introduction: The general symptoms of this disease include progressive loss of memory, changes in behavior, deterioration of thinking, and gradual loss of ability to perform daily activities. According to the World Health Organization, dementia has affected more than 50 million people worldwide, and it is estimated that there are 10 million new cases per year, of which 70% are due to AD. Methods: This paper reported a review of scientific articles available on the internet, which discussed in silico analyzes, such as molecular docking, molecular dynamics, and quantitative structure-activity relationship (QSAR) of different classes of natural products and their derivatives published from 2016 onwards. In addition, this work reports the potential of fermented papaya preparation against oxidative stress in AD. Results: With this research, it is expected that it will highlight the most recent studies about AD, the computational analysis methods used in proposing new bioactive and their possible molecular targets, and finally, the molecules or classes of natural products involved in each study. Conclusion: Thus, studies like this can orientate new works against neurodegenerative diseases, especially AD.

Understanding the quantitative structure–activity relationship of acetylcholinesterase inhibitors for the treatment of Alzheimer's disease

2015 ◽  
Vol 14 (06) ◽  
pp. 1550040 ◽  
Author(s):  
Anuradha Sharma ◽  
Poonam Piplani
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structural Basis ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Qsar Models ◽  
Relationship Of

Alzheimer's disease (AD) is the most common cause of dementia in old aged people and clinically used drugs for treatment are associated with side effects. Thus, there is a current demand for the discovery and development of new potential molecules. However, the recent advances in drug therapy have challenged the predominance of the disease. In this manuscript, an attempt has been made to develop the 2D and 3D quantitative structure–activity relationship (QSAR) models for a series of rutaecarpine, quinazolines and 7,8-dehydrorutaecarpine derivatives to obtain insights to Acetylcholinesterase (AChE) inhibition. Five different QSAR models have been generated and validated using a set of 52 compounds comprising of varying scaffolds with IC50 values ranging from 11,000 nM to 0.6 nM. These AChE-specific prediction models (M1–M5) adequately reflect the structure–activity relationship of the existing AChE inhibitors. Out of all developed models, QSAR model generated using ADME properties has been found to be the best with satisfactory statistical significance (regression (r2) of 0.9309 and regression adjusted coefficient of variation [Formula: see text] of 0.9194). The QSAR models highlight the importance of aromatic moiety as their presence in the structure influence the biological activity. Additional insights on the compounds show that acyclic amines attached to side chain have lower activity than cyclic amines. The QSAR models pinpointing structural basis for the AChEIs suggest new guidelines for the design of novel molecules.

Xanthone: Potential Acetylcholinesterase Inhibitor for Alzheimer's Disease Treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Vincentsia Vienna Vanessa ◽  
Siau Hui Mah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitor ◽  
Structure Activity Relationship ◽  
Acetylcholinesterase Inhibition ◽  
Activity Relationship ◽  
Structure Activity ◽  
Hydrophobic Moiety

: Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer’s treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve the cholinergic postsynaptic transmission. This review highlights a class of heterocycle, namely xanthone and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano and glycosylated xanthones exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine and morpholine have shown greater acetylcholinesterase inhibition activities. Structure-activity relationship of xanthones revealed that the type and position of substituent(s) attached to the xanthone moiety influenced their acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.

scholarly journals Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 350
Author(s):  
Ashwani Arya ◽  
Rubal Chahal ◽  
Rekha Rao ◽  
Md. Habibur Rahman ◽  
Deepak Kaushik ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Activities ◽  
Structural Diversity ◽  
Time Frame ◽  
World Health ◽  
Cholinergic Transmission ◽  
Disease Therapy ◽  
Inhibitory Potential ◽  
Health Organization

Alzheimer’s disease (AD) is a gradually growing irreversible illness of the brain that almost affects every fifth person (aged > 80 years) in the world. World Health Organization (WHO) also revealed that the prevalence of this disease will enhance (upto double) significantly upto 2030. The poor cholinergic transmission at the synapse is considered to be one of the main reasons behind the progression and occurrence of this disorder. Natural inhibitors of acetylcholine (ACh) such as galanthamine and rivastigmine are used commercially in the treatmentof AD. The biomolecules such assesquiterpenes, possess a great structural diversity and are responsible for a plethora of pharmacological properties. The potential of various sesquiterpenes as anticholinesterase has been reviewed in this article. For this purpose, the various databases, mainly PubMed, Scopus, and Web of Science were investigatedwith different keywords such as “sesquiterpenes+acetylcholinesterase” and “sesquiterpenes+cholinesterase+inhibitors” in the surveyed time frame (2010–2020). A vast literature was evident in the last decade, which affirms the potential of various sesquiterpenes in the improvement of cholinergic transmission by inhibiting the AChE. After data analysis, it was found that 12 compounds out of a total of 58 sesquiterpenes were reported to possess IC50 < 9μM and can be considered as potential candidates for the improvement of learning and memory. Sesquiterpene is an important category of terpenoids, found to possess a large spectrum of biological activities. The outcome of the review clearly states that sesquiterpenes (such as amberboin, lipidiol,etc) from herbs could offer fresh, functional compounds for possible prevention and treatment of AD.

scholarly journals A Review on Biological Activity of Heterocyclic Nucleus Carbazole

2020 ◽  
Vol 8 (3) ◽  
pp. 152-161
Author(s):  
Monika Meghani ◽  
Pawan Kumar Mahawar ◽  
Kapil Sharma ◽  
Gurvindar Singh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Delivery System ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Senile Dementia ◽  
Polymeric Nanoparticles ◽  
Molecular Complexes ◽  
Nano Particles ◽  
World Health

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with cognitive deterioration affecting day to day living and behavioural activities. It is commonest cause of senile and pre-senile dementia. In Alzheimer’s disease, a peptide referred as amyloid beta aggregates (oligomers), and accumulates in the brain to form deposits called as amyloid plaques. According to the world health organization (WHO), 5% of men and 6% of women of above 60 years are victims with Alzheimer’s type dementia globally. In India prevalence of dementia is 33.6%, of which AD contributes approximately 54% and vascular dementia constitutes approximately 39%. Patients with the prolonged use of some Non-steroidal anti-inflammatory (NSAID) drugs such as ibuprofen have lower risk of developing the symptoms of AD; however the chronic use of NSAID can produce a toxic effect on the kidney, liver and GI tract. Recent studies have demonstrated that a curcumin delivery system based on nanoscience and nanotechnology increases the therapeutic potential of this compound. Specifically, several nano-sized carriers such as phospholipid vesicles (liposomes), micelles, solid lipid nanoparticles, polymeric nanoparticles, emulsions, proteins and other molecular complexes have been developed for the efficient delivery of curcumin. Nano particles have demonstrated the enhanced Bioavailability of curcumin including circulation time in the blood. Various nano technology drug delivery system of curcumin showed increased Bio accessibility during treatment of Alzheimer’s disease.  

scholarly journals Comparison Study of Various Nano Technology Formulation of Curcumin in Treatment of Alzheimer’s Disease

2020 ◽  
Vol 8 (3) ◽  
pp. 99-103
Author(s):  
Mahaveer Singh ◽  
Kushali D ◽  
Vinay C H
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Delivery System ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Senile Dementia ◽  
Molecular Complexes ◽  
Nano Particles ◽  
World Health ◽  
Nano Technology

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with cognitive deterioration affecting day to day living and behavioural activities. It is commonest cause of senile and pre-senile dementia. In Alzheimer’s disease, a peptide referred as amyloid beta aggregates (oligomers), and accumulates in the brain to form deposits called as amyloid plaques. According to the world health organization (WHO), 5% of men and 6% of women of above 60 years are victims with Alzheimer’s type dementia globally. In India prevalence of dementia is 33.6%, of which AD contributes approximately 54% and vascular dementia constitutes approximately 39%. Patients with the prolonged use of some Non-steroidal anti-inflammatory (NSAID) drugs such as ibuprofen have lower risk of developing the symptoms of AD; however the chronic use of NSAID can produce a toxic effect on the kidney, liver and GI tract. Recent studies have demonstrated that a curcumin delivery system based on nanoscience and nanotechnology increases the therapeutic potential of this compound. Specifically, several nano-sized carriers such as phospholipid vesicles (liposomes), micelles, solid lipid nanoparticles, polymeric nanoparticles, emulsions, proteins and other molecular complexes have been developed for the efficient delivery of curcumin. Nano particles have demonstrated the enhanced Bioavailability of curcumin including circulation time in the blood. Various nano technology drug delivery system of curcumin showed increased Bio accessibility during treatment of Alzheimer’s disease.  

scholarly journals Terpenes: Natural Products for Controlling Insects of Importance to Human Health—A Structure-Activity Relationship Study

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
José S. Dambolena ◽  
María P. Zunino ◽  
Jimena M. Herrera ◽  
Romina P. Pizzolitto ◽  
Vanessa A. Areco ◽  
...  
Keyword(s):  
Natural Products ◽  
Human Health ◽  
Insecticidal Activity ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Qsar Analysis ◽  
Qsar Studies ◽  
Development Of Resistance ◽  
Structure Activity

Many insects affect food production and human health, and in an attempt to control these insects the use of synthetic insecticides has become widespread. However, this has resulted in the development of resistance in these organisms, human diseases, contamination of food, and pollution of the environment. Plants natural products and essential oil components such as terpenes and phenylpropenes have been shown to have a significant potential for insect control. However, the molecular properties related to their insecticidal activity are not well understood. The purpose of this review is to provide an overview of the toxicity of terpene compounds against three insects of importance to human health: lice, cockroaches, and Triatominae bugs and to evaluate which molecular descriptors are important in the bioactivity of terpenes. For the insects studied, quantitative structure-activity relationship (QSAR) studies were performed in order to predict the insecticidal activity of terpene compounds. The obtained QSAR models indicated that the activity of these compounds depends on their ability to reach the targets and to interact with them. The QSAR analysis can be used to predict the bioactivities of other structurally related molecules. Our findings may provide an important contribution in the search for new compounds with insecticidal activity.

Pakistan

2019 ◽  
pp. 61-78 ◽  
Author(s):  
Muhammad Nasar Sayeed Khan ◽  
Muhammad Iqbal Afridi ◽  
Afzel Javed
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Memory Loss ◽  
Developed Countries ◽  
World Health ◽  
Average Life Expectancy ◽  
People With Dementia ◽  
Health Organization ◽  
Number Of Individuals

Pakistan is one of the largest and most populated nations of South Asia and ranked sixth among the most crowded countries in the world, with a population exceeding 196 million. Because of a lack of research and the cultural setting, it is exceptionally hard to obtain an exact number of individuals suffering from dementia. However, the extrapolated prevalence of people with dementia in Pakistan is around 200,000. Compared to developed countries, only 4.2% of the Pakistani population are aged above 65 years, possibly due to an average life expectancy of 66 years for both genders . Although no specific data on elderly people with dementia in Pakistan are available, it is estimated that 8–10% of the general population aged above 65 years suffer from chronic memory loss. According to the latest 2014 World Health Organization data, Alzheimer’s disease/dementia-related deaths in Pakistan reached a total of 1776 or 0.16% of total deaths. Pakistan currently has the largest generation of young people ever recorded in its history, who will be at risk for dementia and Alzheimer’s disease by 2050, at which time, life expectancy would be expected to continue rising. Thus, the economic burden of treating patients with Alzheimer’s disease and other types of dementia will increase considerably.

Diagnosis of Alzheimer's Disease

1997 ◽  
Vol 9 (S1) ◽  
pp. 5-7 ◽  
Author(s):  
Barry Reisberg ◽  
Alistair Burns
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
World Health Organization ◽  
World Health ◽  
European Federation ◽  
The World ◽  
Health Organization ◽  
Special Meeting

This issue on the diagnosis of Alzheimer's disease (AD) is the product of a special meeting of the International Psychogeriatric Association with the cosponsorship of Alzheimer's Disease International, the European Federation of Neurological Societies, the World Health Organization, and the World Psychiatric Association. The meeting was held in Geneva, Switzerland, from November 10 to 12, 1996. Participants included many of the leading experts on the various aspects of AD diagnosis as well as clinical experts, general experts in the field of AD, organizational representatives, and outstanding clinician-scientists who served as facilitators and in other capacities.

scholarly journals Preparation of 4-Flexible Amino-2-Arylethenyl-Quinoline Derivatives as Multi-target Agents for the Treatment of Alzheimer’s Disease

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3100 ◽  
Author(s):  
Xiao-Qin Wang ◽  
Chu-Ping Zhao ◽  
Long-Cheng Zhong ◽  
De-Ling Zhu ◽  
De-Hao Mai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Aged People ◽  
Structure Activity ◽  
Aβ Aggregation ◽  
Aggregation Inhibition ◽  
Low Toxicity ◽  
Multifunctional Agents

Alzheimer’s disease (AD) is a complex and multifactorial neurodegenerative disorder of aged people. The development of multitarget-directed ligands (MTDLs) to act as multifunctional agents to treat this disease is the mainstream of current research. As a continuation of our previous studies, a series of 4-flexible amino-2-arylethenylquinoline derivatives as multi-target agents was efficiently synthesized and evaluated for the treatment of AD. Among these synthesized derivatives, some compounds exhibited strong self-induced Aβ1–42 aggregation inhibition and antioxidant activity. The structure-activity relationship was summarized, which confirmed that the introduction of a flexible amino group featuring a N,N-dimethylaminoalkylamino moiety at the 4-position increased the Aβ1–42 aggregation inhibition activity, with an inhibition ratio of 95.3% at 20 μM concentration. Compound 6b1, the optimal compound, was able to selectively chelate copper (II), and inhibit Cu2+-induced Aβ aggregation effectively. It also could disassemble the self-induced Aβ1–42 aggregation fibrils with a ratio of 64.3% at 20 μM concentration. Moreover, compound 6b1 showed low toxicity and a good neuroprotective effect against Aβ1–42-induced toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated compound 6b1 significantly reversed scopolamine-induced memory deficit in mice. Taken together, these results suggested that compound 6b1 was a promising multi-target compound worthy of further study for AD.

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