Molecular Docking and Dynamic Simulation of AZD3293 and Solanezumab Effects Against BACE1 to Treat Alzheimer's Disease

Amyloidogenesis is the process in which amyloid beta (Aβ) peptide aggregation results in plaque formation in central nervous system (CNS) are associated with many neurological diseases such as Alzheimer’s disease. The peptide aggregation initiated from peptide monomers results in formation of dimers, tetramers, fibrils, and protofibrils. The ability of allicin, a lipid-soluble volatile organosulfur biological compound, present in freshly crushed garlic ( Allium sativum L.) to inhibit fibril formation by the Aβ peptide in vitro was investigated in the present study. Inhibition of fibrillogenesis was measured by a Thioflavin T (ThT) fluorescence assay and visualized by transmission electron microscopy (TEM). The molecular interaction between allicin and Aβ peptide was also demonstrated by in silico studies. The results show that allicin strongly inhibited Aβ fibrils by 97% at 300 µM, compared with control (Aβ only) ( P < .001). These results were further validated by visual of fibril formation by transmission microscopy and molecular interaction of amyloid peptide with allicin by molecular docking. Aβ forms favourable hydrophobic interaction with Ile32, Met35, Val36, and Val39, and oxygen of allicin forms hydrogen bond with the amino acid residue Lys28. Allicin anti-amyloidogenic property suggests that this naturally occurring compound may have potential to ameliorate and prevent Alzheimer’s disease.

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MOLECULAR DOCKING STUDIES ON THE THERAPEUTIC TARGETS OF ALZHEIMER'S DISEASE (AChE AND BChE) USING NATURAL BIOACTIVE ALKALOIDS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i12.14833 ◽

2016 ◽

Vol 8 (12) ◽

pp. 108

Author(s):

Punabaka Jyothi ◽

Kuna Yellamma

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Binding Affinity ◽

Neurodegenerative Disorder ◽

Biological Activities ◽

Neuropsychiatric Symptoms ◽

Docking Studies ◽

Kcal Mole ◽

Molecular Docking Studies

Objective: Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms, is biochemically characterized by a significant decrease in the brain neurotransmitter Acetylcholine (ACh).Methods: In the present insilico study, six plant bioactive compounds namely Harmol, Vasicine, Harmaline, Harmine, Harmane and Harmalol (from P. Nigellastrum Bunge) were analyzed for their inhibitory role on AChE (Acetylcholinesterase) and BChE (Butyrylcholinesterase) activity by applying the molecular docking studies. Other parameters viz. determination of molecular interaction-based binding affinity values, protein-ligand interactions, Lipinski rule of five, functional properties and biological activities for the above compounds were also calculated by employing the appropriate bioinformatics tools.Results: The results of docking analysis clearly showed that Harmalol has highest binding affinity with AChE (-8.6 kcal/mole) and BChE (-8.0 kcal/mole) but it does not qualified the enzyme inhibitory activity, since it was exerted, and also has least percentage activity on AD and neurodegenerative disease. Whereas, the Harmine has been second qualified binding affinity (-8.4 kcal/mol) and first in other parameters when compared with Harmalol.Conclusion: Based on docking results and other parameters conducted, we are concluding that Harmine is the best compound for further studies to treat AD.Keywords: Alzheimer's disease (AD), Acetylcholinesterase, Butyrylcholinesterase, Lead Molecules

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Insilico Molecular Docking of some Isolated Selected Compounds of Lantana Camera against Alzheimer’s Disease

Biomedical Journal of Scientific & Technical Research ◽

10.26717/bjstr.2018.12.002235 ◽

2018 ◽

Vol 12 (2) ◽

Author(s):

Mohuya Majumder

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking

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Kinetics and Molecular Docking Study of an Anti-diabetic Drug Glimepiride as Acetylcholinesterase Inhibitor: Implication for Alzheimer’s Disease-Diabetes Dual Therapy

Neurochemical Research ◽

10.1007/s11064-016-1859-3 ◽

2016 ◽

Vol 41 (6) ◽

pp. 1475-1482 ◽

Cited By ~ 12

Author(s):

Syed Mohd. Danish Rizvi ◽

Sibhghatulla Shaikh ◽

Deeba Naaz ◽

Shazi Shakil ◽

Adnan Ahmad ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Acetylcholinesterase Inhibitor ◽

Dual Therapy ◽

Docking Study ◽

Molecular Docking Study

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Neuroprotective effects of bergenin in Alzheimer’s disease: Investigation through molecular docking, in vitro and in vivo studies

Behavioural Brain Research ◽

10.1016/j.bbr.2018.08.010 ◽

2019 ◽

Vol 356 ◽

pp. 18-40 ◽

Cited By ~ 21

Author(s):

Priyal Barai ◽

Nisith Raval ◽

Sanjeev Acharya ◽

Ankit Borisa ◽

Hardik Bhatt ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

In Vivo Studies ◽

Neuroprotective Effects

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Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation

Molecules ◽

10.3390/molecules25092071 ◽

2020 ◽

Vol 25 (9) ◽

pp. 2071

Author(s):

Syed Sayeed Ahmad ◽

Meetali Sinha ◽

Khurshid Ahmad ◽

Mohammad Khalid ◽

Inho Choi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Md Simulation ◽

Simulation Analysis ◽

Dynamics Simulation ◽

Caspase 8 ◽

Amino Acid Residues ◽

The Stability ◽

Molecular Docking And Dynamics

Alzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (−6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8–rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer’s potential against caspase 8.

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