Homology Modeling and in silico docking analysis of BDNF in the treatment of Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia and one of the leading causes of death. The Aim and objective of the present study is to perform in-silico docking analysis of the major active constituents identified in three Indian medicinal plants namely Convolvulus pluricaulis, Coriandrum sativum and Panax ginseng for its effectiveness against the targets of Alzheimer Disease. In-silico docking analysis was performed by Molegro Virtual Docker (MVD-2010, 4.2.0) and Schrodinger Mestro (V 11.8). In addition, Drug likeness property, pharmacokinetics (ADME) and safety profile prediction studies were performed to identify the best drug candidates using Qikpro and Toxicity Estimation Software Tool (T.E.S.T). The target for Alzheimer Disease is Acetylcholinesterase and Butyrylcholinesterase. The X-ray crystal co-ordinates of AChE (PDB ID: 4bdt) and BChE (PDB ID: 6eqq) obtained from the Protein Data Bank. The phytoconstituents of three medicinal plants were retrieved from PubChem compound database in mol format. The standard drugs Donepezil, Rivastigmine, Galantamine, Memantine was obtained from the drug bank in .mol format for comparison. It was analysed from the parameters of docking that the phytoconstituents from Panax ginseng showed better anti-Alzheimer activity compared to that of the standard drugs. Based on the research findings, further studies can be performed in in-vitro & in-vivo animal models of Alzheimer’s disease to establish the efficacy of promising phytoconstituents.

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Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502015000100006 ◽

2015 ◽

Vol 51 (1) ◽

pp. 53-61 ◽

Cited By ~ 2

Author(s):

Muhammad Yar ◽

Muhammad Arshad ◽

Ariba Farooq ◽

Mazhar Amjad Gilani ◽

Khurshid Ayub ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Free Radicals ◽

In Silico ◽

Density Functional ◽

Neurodegenerative Disorder ◽

Antioxidant Properties ◽

Docking Studies ◽

In Silico Docking ◽

Ic50 Values

Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential.

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In Silico Homology Modeling of Presenilin 2-Therapeutic Target for Alzheimer's disease

Research Journal of Pharmacy and Technology ◽

10.5958/0974-360x.2019.00575.4 ◽

2019 ◽

Vol 12 (7) ◽

pp. 3405

Author(s):

Sowmya Hari ◽

S. Akilashree

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Homology Modeling ◽

Therapeutic Target ◽

In Silico ◽

Presenilin 2

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In silico Docking Studies and Potential Lead Identification against JNK3 for Alzheimer’s Disease

International Journal of Pharmaceutical Investigation ◽

10.5530/ijpi.2019.4.41 ◽

2019 ◽

Vol 9 (4) ◽

pp. 220-222

Author(s):

Nishtha Singh ◽

Sonal Upadhyay ◽

Ankur Jaiswar ◽

Nidhi Mishra

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

In Silico ◽

Docking Studies ◽

In Silico Docking ◽

Lead Identification

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Phytochemicals for drug discovery in Alzheimer’s disease: In silico Advances

Current Pharmaceutical Design ◽

10.2174/1381612826666200928161721 ◽

2020 ◽

Vol 26 ◽

Author(s):

Smriti Sharma ◽

Vinayak Bhatia

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Drug Design ◽

In Silico ◽

Drug Targets ◽

Development Process ◽

Phytochemical Analysis ◽

Computational Drug Design ◽

Novel Drugs ◽

Game Changer

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

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

Central Nervous System Agents in Medicinal Chemistry ◽

10.2174/1871524920666201119144535 ◽

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.

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