In-silico study of some natural plant phyto-compounds for the identification of novel potent cholinesterase inhibitors against Alzheimer's Disease

2021 ◽  
Vol 12 (3) ◽  
pp. 243-250
Author(s):  
Dhiraj Kumar ◽  
Sanjana Bhagat
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Binding Affinity ◽  
In Silico ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Ache Inhibitor ◽  
Strong Binding ◽  
In Silico Studies ◽  
Autodock 4.0

The main aim of this study is to identify inhibitory binding potent of the available commercially alkaloids, against the crystal structure of acetylcholinesterase (AChE) protein by in silico studies. The inhibitory data of the compounds should be compared with the internal ligand as well as standard AChE inhibitor Aricept (which is used for the treatment of all stages of Alzheimer’s disease). AutoDock 4.0 is used for the docking study, conformational orientation site analysis, and, with the help of docking, we have calculated parameters like binding energy and inhibition constant. Docking's study showed that Glabridin, Isorosmanol, Quercetin, Honokiol, Eckol, Sargaquinoic acid, and Ginsedosides revealed strong binding affinity with the enzyme. Moreover, The ADMET profiling and physicochemical properties of the selected compounds are evaluated using the Molinspiration and Data warrior software. By showing a strong binding affinity value, positive bioactivity score, and good pharmacokinetic properties, the top compound was determined. After evaluation with all parameters, the compound Glabridin and Ginsedosides show the most potent inhibitory effect towards the acetylcholinesterase, so this compound could be used as a novel is required to treat Alzheimer's disease.

scholarly journals In-Silico Study of Some Natural Plant Phyto-compounds for the Identification of Novel Potent Cholinesterase Inhibitors Against Alzheimer Disease

2021 ◽  
Author(s):  
Dhiraj Kumar ◽  
Sanjana Bhagat
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Ache Inhibitor ◽  
Site Analysis ◽  
Strong Binding ◽  
In Silico Studies ◽  
Potent Inhibitory Effect ◽  
Autodock 4.0

The main aim of this study is to identify inhibitory binding potent of the available commercially alkaloids, against the crystal structure of acetylcholinesterase (AChE) protein by in silico studies. The inhibitory data of the compounds should be compared with the internal ligand as well as standard AChE inhibitor Aricept (which is used for the treatment of all stages of Alzheimer’s disease). AutoDock 4.0 is used for the docking study, conformational orientation site analysis, and, with the help of docking, we have calculated parameters like binding energy and inhibition constant. Docking's study showed that Glabridin, Isorosmanol, Quercetin, Honokiol, Eckol, Sargaquinoic acid, and Ginsedosides revealed strong binding affinity with the enzyme. Moreover, The ADMET profiling and physicochemical properties of the selected compounds are evaluated using the Molinspiration and Data warrior software. By showing a strong binding affinity value, positive bioactivity score, and good pharmacokinetic properties, the top compound was determined. After evaluation with all parameters, the compound Glabridin and Ginsedosides show the most potent inhibitory effect towards the acetylcholinesterase, so this compound could be used as a novel is required to treat Alzheimer's disease.

Lepidine B from Lepidium Sativum Seeds as Multi-Functional Anti-Alzheimer’s Disease Agent: In Vitro and In Silico Studies

2020 ◽  
Vol 16 ◽  
Author(s):  
Talia Serseg ◽  
Khedidja Benarous ◽  
Meriem Lamrani ◽  
Mohamed Yousfi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Lepidium Sativum ◽  
Drug Candidate ◽  
Juniperus Oxycedrus ◽  
In Silico Studies ◽  
Juniperus Phoenicea

Objective: The present study is carried out to screen the anticholinesterase effect of the total alkaloids of L. sativum seeds and other plants, and studied the ability of Lepidine B to inhibit AChE, BuChE, BACE and MAGL. and the main interactions in inhibitor-enzyme complex. Method: Inhibitory effect extracts from Lepidium sativum, Juniperus phoenicea and Juniperus oxycedrus on acetylcholinesterase using Ellman method have been investigated using Donepezil as positive control. Molecular docking study carried out using Autodock vina. The structures of studied molecules Lepidine B, Galantamine and Donepezil were obtained from PubChem database and Protein databank. Results: Alkaloidal extract of Lepidium sativum and ethyl acetate extracts of Juniperus phoenicea and Juniperus oxycedrus exhibit a strong acetylcholinesterase inhibitory activity with IC50 values of 0.59 ± 0.04, 0.57 ± 0.00 and 0.49 ± 0.00 mg/mL, respectively using Donepezil <0.25 mg/mL as positive control. The major component of alkaloid of L. sativum, Lepidine B bind so tightly to AChE and BuChE as much as galantamine and donepezil. We suggest that Lepidine B is a non-competitive inhibitory by interacting with PAS of AChE and BuChE, therefore it is capable to prevent the HuAChE-induced Aβ aggregation. We have found significant interactions in the Lepidine B-BACE and Lepidine B-MAGL complexes. Conclusion: The docking study indicate that Lepidine B is a promising anti-AD drug and might become a drug candidate to prevent Alzheimer's disease due to its multiple roles as potent inhibitor for AChE, BuChE, BACE and MAGL, also inhibitor for Aβ fibrillogenesis. No previous results about the inhibitory effect Lepidine B on the AChE, BuChE, β secretase and monoacylglycerol lipase have been reported.

Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

2019 ◽  
Vol 15 (4) ◽  
pp. 373-382 ◽  
Author(s):  
Ralph C. Gomes ◽  
Renata P. Sakata ◽  
Wanda P. Almeida ◽  
Fernando Coelho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Population Aging ◽  
Acetylcholinesterase Inhibitors ◽  
Acetylcholinesterase Activity ◽  
Docking Study ◽  
Biological Properties ◽  
Ache Inhibitor ◽  
Molecular Docking Study

Background: The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease. Methods: The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase. Results: Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Conclusion: We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.

In silico screening of pyridoxine carbamates for Anti-Alzheimer’s activities

2020 ◽  
Vol 20 ◽  
Author(s):  
Dnyaneshwar Baswar ◽  
Abha Sharma ◽  
Awanish Mishra
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Neurodegenerative Disorder ◽  
Biological Activities ◽  
Cholinergic Neurons ◽  
In Silico Screening ◽  
In Silico Studies ◽  
Bbb Permeability ◽  
Ld50 Value

Background: Alzheimer’s disease (AD), an irreversible complex neurodegenerative disorder, is most common type of dementia, with progressive loss of cholinergic neurons. Based on the multi- factorial etiology of Alzheimer’s disease, novel ligands strategy appears as up-coming approach for the development of newer molecules against AD. This study is envisaged to investigate anti-Alzheimer’s potential of 10 synthesized compounds. The screening of compounds (1-10) was carried out using in silico techniques. Methods: For in silico screening of physicochemical properties of compounds molinspiration property engine v.2018.03, Swiss ADME online web-server and pkCSM ADME were used. For pharmacodynamic prediction PASS software while toxicity profile of compounds were analyzed through ProTox-II online software. Simultaneously, molecular docking analysis was performed on mouse AChE enzyme (PDB ID:2JGE, obtained from RSCB PDB) using Auto Dock Tools 1.5.6. Results: Based on in silico studies, compound 9 and 10 have been found to have better drug likeness, LD50 value, and better anti-Alzheimer’s, nootropic activities. However, these compounds had poor blood brain barrier (BBB) permeability. Compound 4 and 9 were predicted with better docking score for AChE enzyme. Conclusion: The outcome of in silico studies have suggested, out of various substitutions at different positions of pyridoxine-carbamate, compound 9 have shown promising drug likeness, with better safety and efficacy profile for anti-Alzheimer’s activity. However, BBB permeability appears as one the major limitation of all these compounds. Further studies are required to confirm its biological activities.

scholarly journals β-Carotene: A Natural Compound Improves Cognitive Impairment and Oxidative Stress in a Mouse Model of Streptozotocin-Induced Alzheimer’s Disease

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 441 ◽  
Author(s):  
Sundas Hira ◽  
Uzma Saleem ◽  
Fareeha Anwar ◽  
Muhammad Farhan Sohail ◽  
Zohaib Raza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Control Group ◽  
Enhancement Effect ◽  
Amyloid Β Protein ◽  
Group I ◽  
In Silico Studies ◽  
Β Carotene

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a cascade of changes in cognitive, behavioral, and social activities. Several areas of the brain are involved in the regulation of memory. Of most importance are the amygdala and hippocampus. Antioxidant therapy is used for the palliative treatment of different degenerative diseases like diabetes, cirrhosis, and Parkinson’s, etc. The objective of this study was to assess the effectiveness of exogenous antioxidants, in particular, β carotene (1.02 and 2.05 mg/kg) against intracerebroventricular injected streptozotocin-induced memory impairment in mice. Streptozotocin (3 mg/kg, i.c.v) was administered in two separate doses (on 1st and 3rd days of treatment) for neurodegeneration. Fifty Albino mice (male) were selected in the protocol, and they were classified into five groups (Group I—control, Group II—disease, Group III—standard, Group IV–V—β-carotene-treated) to investigate the cognitive enhancement effect of selected antioxidants. The cognitive performance was observed following the elevated plus-maze, passive avoidance, and open field paradigms. Acetylcholine esterase, β-amyloid protein, and biochemical markers of oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase were analyzed in brain homogenates. In silico activity against acetylcholinesterase (AChE) was determined by the molecular modeling of β-carotene. β-carotene at a dose of 2.05 mg/kg was found to attenuate the deleterious effects of streptozotocin-induced behavioral and biochemical impairments, including the inhibition of acetylcholinesterase activity. The in silico studies confirmed the binding capacity of β-carotene with the acetylcholinesterase enzyme. The administration of β-carotene attenuated streptozotocin-induced cognitive deficit via its anti-oxidative effects, inhibition of acetylcholinesterase, and the reduction of amyloid β-protein fragments. These results suggest that β-carotene could be useful for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

scholarly journals Anticholinesterase Activity of Eight Medicinal Plant Species: In Vitro and In Silico Studies in the Search for Therapeutic Agents against Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Md Josim Uddin ◽  
Daniela Russo ◽  
Md Mahbubur Rahman ◽  
Shaikh Bokhtear Uddin ◽  
Mohammad A. Halim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medicinal Plant ◽  
Plant Species ◽  
Inhibitory Effect ◽  
Medicinal Plant Species ◽  
Inhibitory Effects ◽  
In Silico Studies ◽  
Blumea Lacera

Many Bangladeshi medicinal plants have been used to treat Alzheimer’s disease and other neurodegenerative diseases. In the present study, the anticholinesterase effects of eight selected Bangladeshi medicinal plant species were investigated. Species were selected based on the traditional uses against CNS-related diseases. Extracts were prepared using a gentle cold extraction method. In vitro cholinesterase inhibitory effects were measured by Ellman’s method in 96-well microplates. Blumea lacera (Compositae) and Cyclea barbata (Menispermaceae) were found to have the highest acetylcholinesterase inhibitory (IC50, 150 ± 11 and 176 ± 14 µg/mL, respectively) and butyrylcholinesterase inhibitory effect (IC50, 297 ± 13 and 124 ± 2 µg/mL, respectively). Cyclea barbata demonstrated competitive inhibition, where Blumea lacera showed an uncompetitive inhibition mode for acetylcholinesterase. Smilax guianensis (Smilacaceae) and Byttneria pilosa (Malvaceae) were also found to show moderate AChE inhibition (IC50, 205 ± 31 and 221 ± 2 µg/mL, respectively), although no significant BChE inhibitory effect was observed for extracts from these plant species. Among others, Thunbergia Grandiflora (Acanthaceae) and Mikania micrantha (Compositae) were found to display noticeable AChE (IC50, 252 ± 22 µg/mL) and BChE (IC50, 314 ± 15 µg/mL) inhibitory effects, respectively. Molecular docking experiment suggested that compounds 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone (BL4) and kaempferol-3-O-α-L-rhamnopyranosyl-(1⟶6)-β-D-glucopyranoside (BL5) from Blumea lacera bound stably to the binding groove of the AChE and BChE by hydrogen-bond interactions, respectively. Therefore, these compounds could be candidates for cholinesterase inhibitors. The present findings demonstrated that Blumea lacera and Cyclea barbata are interesting objects for further studies aiming at future therapeutics for Alzheimer’s disease.

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