scholarly journals Chemical Constituents from the Wild Atractylodes macrocephala Koidz and Acetylcholinesterase Inhibitory Activity Evaluation as Well as Molecular Docking Study

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7299
Author(s):  
Qiannan Zhu ◽  
Min Lin ◽  
Wanying Zhuo ◽  
Yunzhi Li
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Chemical Constituents ◽  
Colorimetric Method ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Catalytic Active Site ◽  
Important Trend ◽  
Atractylodes Macrocephala ◽  
Dual Site

Screening the lead compounds which could interact both with PAS and CAS of acetylcholinesterase (AChE) is an important trend in finding innovative drugs for Alzheimer’s disease (AD). In this paper, four sesquiterpenes, i.e., atractylenolide III (1), atractylenolide IV (2), 3-acetyl-atractylon (3) and β-eudesmol (4), were obtained from the wild Atractylode macrocephala grown in Qimen for the first time. Their structures were elucidated mainly by NMR spectroscopy. To screen the potential dual site inhibitors of AChE, the compounds 1, 2, 3, as well as a novel and rare bisesquiterpenoid lactone, biatractylenolide II (5), which was also obtained from the tilted plant in our previous investigation, were evaluated their AChE inhibitory activities by using Ellman’s colorimetric method. The results showed that biatractylenolide II displayed moderate inhibitory activity (IC50 = 19.61 ± 1.11 μg/mL) on AChE. A further molecular docking study revealed that biatractylenolide II can interact with both the peripheral anionic site (PAS) and the catalytic active site (CAS) of AChE. These data suggest that biatractylenolide II can be considered a new lead compound to research and develop more potential dual site inhibitors of AChE.

scholarly journals An Antioxidant Potential, Quantum-Chemical and Molecular Docking Study of the Major Chemical Constituents Present in the Leaves of Curatella americana Linn

2018 ◽  
Vol 11 (3) ◽  
pp. 72 ◽  
Author(s):  
Mayara Teles Fujishima ◽  
Nayara Silva ◽  
Ryan Ramos ◽  
Elenilze Batista Ferreira ◽  
Kelton Santos ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Xanthine Oxidase ◽  
Quantum Chemical ◽  
Binding Free Energy ◽  
Chemical Constituents ◽  
Docking Study ◽  
Antioxidant Potential ◽  
Molecular Docking Study ◽  
Hydroalcoholic Extract ◽  
Curatella Americana

Reactive oxygen species (ROS) are continuously generated in the normal biological systems, primarily by enzymes as xanthine oxidase (XO). The inappropriate scavenging or inhibition of ROS has been considered to be linked with aging, inflammatory disorders, and chronic diseases. Therefore, many plants and their products have been investigated as natural antioxidants for their potential use in preventive medicine. The leaves and bark extracts of Curatella americana Linn. were described in scientific research as anti-inflammatory, vasodilator, anti-ulcerogenic, and hypolipidemic effects. So, the aim of this study was to evaluate the antioxidant potentials of leaf hydroalcoholic extract from C. americana (HECA) through the scavenging DPPH assay and their main chemical constituents, evaluated by the following quantum chemical approaches (DFT B3LYP/6-31G**): Maps of Molecular Electrostatic Potential (MEP), Frontier Orbital’s (HOMO and LUMO) followed by multivariate analysis and molecular docking simulations with the xanthine oxidase enzyme. The hydroalcoholic extract showed significant antioxidant activity by free radical scavenging probably due to the great presence of flavonoids, which were grouped in the PCA and HCA analysis with the standard gallic acid. In the molecular docking study, the compounds studied presented the binding free energy (ΔG) values close each other, due to the similar interactions with amino acids residues at the activity site. The descriptors Gap and softness were important to characterize the molecules with antioxidant potential by capturing oxygen radicals.

Synthesis, molecular docking study and thymidine phosphorylase inhibitory activity of 3-formylcoumarin derivatives

2018 ◽  
Vol 78 ◽  
pp. 17-23 ◽  
Author(s):  
Muhammad Taha ◽  
Syed Adnan Ali Shah ◽  
Muhammad Afifi ◽  
Syahrul Imran ◽  
Sadia Sultan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Thymidine Phosphorylase ◽  
Docking Study ◽  
Molecular Docking Study

scholarly journals Acetylcholinesterase and Cytotoxic Activity of Chemical Constituents of Clutia lanceolata Leaves and its Molecular Docking Study

2016 ◽  
Vol 6 (6) ◽  
pp. 267-278 ◽  
Author(s):  
Mehtab Parveen ◽  
Faheem Ahmad ◽  
Ali Mohammed Malla ◽  
Shaista Azaz ◽  
Mahboob Alam ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cytotoxic Activity ◽  
Chemical Constituents ◽  
Docking Study ◽  
Molecular Docking Study

Identification of Human Acetylcholinesterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations

2018 ◽  
Vol 21 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Lihu Zhang ◽  
Dongdong Li ◽  
Fuliang Cao ◽  
Wei Xiao ◽  
Linguo Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Serine Proteases ◽  
Colorimetric Method ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ache Inhibitors ◽  
Starting Point

Aim and Objective: EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial role in the treatment of multiple diseases, particularly Alzheimer's disease (AD). Identification of natural acetylcholinesterase (AChE) inhibitors from EGb761 would provide a novel therapeutic approach against the Alzheimer's disease. Material and Method: A series of 21 kinds of promising EGb761 compounds were selected, and subsequently evaluated for their potential ability to bind AChE enzyme by molecular docking and a deep analysis of protein surface pocket features. Results: Docking results indicated that these compounds can bind tightly with the active site of human AChE, with favorable distinct interactions around several important residues Asp74, Leu289, Phe295, Ser293, Tyr341, Trp286 and Val294 in the active pocket. Most EGB761 compounds could form the hydrogen bond interactions with the negatively charged Asp74 and Phe295 residues. Among these compounds, diosmetin is the one with the best-predicted docking score while three key hydrogen bonds can be formed between small molecule and corresponding residues of the binding site. Besides, other three compounds luteolin, apigenin, and isorhamnetin have better predicted docking scores towards AChE than other serine proteases, i.e Elastase, Tryptase, Factor XA, exhibiting specificity for AChE inhibition. The RMSD and MM-GBSA results from molecular dymamic simulations indicated that the docking pose of diosmetin-AChE complex displayed highly stable, which can be used for validating the accuracy of molecular docking study. Subsequently, the AChE inhibitory activities of these compounds were evaluated by the Ellman's colorimetric method. Conclusion: The obtained results revealed that all the four compounds exhibited modest AChE inhibitory activity, among which Diosmetin manifested remarkable anti-AChE activity, comparable with the reference compound, Physostigmine. It can be deduced that these EGB761 compounds can be regarded as a promising starting point for developing AChE inhibitors against AD.

scholarly journals Putative Molecular Mechanisms of Neuroprotective Cerebrosides and Their Docking Studies on Acetyl Cholinesterase Enzyme Inhibition for the Treatment of Alzheimer’s Disease

2021 ◽  
Author(s):  
SHAIK IBRAHIM KHALIVULLA ◽  
Kokkanti Mallikarjuna
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Enzyme Inhibition ◽  
Docking Study ◽  
Tau Proteins ◽  
World Health ◽  
Molecular Docking Study ◽  
Ache Inhibitors ◽  
Catalytic Active Site

Abstract The Dementia disease is characterised by neuropsychiatric disturbances due to lack of proper synaptic communication between neurons causing the cognitive behavioural problems. The Alzheimer’s disease (AD) in elderly population is one of the several forms of Dementia. Recent data by World Health Organisation indicates that nearly 10 million people are getting dementia every year, of which 60-70% accounts for AD. The etiology of AD involves the formation of amyloid-β plaques and neurofibrillary Tau tangles in the brain resulting in the death of neural cells. There is no permanent solution for AD treatment, except the FDA approved drugs like galantamine, donepezil, rivastigmine and memantine that are normally associated with side effects. At this juncture, cerebrosides, the natural secondary metabolites identified from different taxa with potential neuroprotective effects offer a promising scope for the treatment of AD. In this paper, cerebrosides reported from all taxa are pooled up along with their functions and listed. The review of literature revealed that Cerebrosides can increase the cognitive functions by regulating or interacting with the N-methyl-d-aspartate (NMDA) calcium ion (Ca2+) channels at post-synaptic receptor; nitric oxide (NO); Bcl2, Bax, amyloid precursor (APP) and Tau proteins; brain-derived neurotrophic factor (BDNF) and cAMP- response element-binding proteins (CREB).This indicates that the Cerebrosides could be potential therapeutic agents for the protection of neurons involved in neurodegenerative disease like Alzheimer’s disease. The current neuroprotective drugs are AChE inhibitors; hence, in the present investigation, in silico molecular docking study on cerebrosides for the inhibition of AChE was assessed to find out their capacity to interact with an active catalytic site of AChE. The results of present investigation revealed that all 22 cerebrosides selected for this work interacted with catalytic active site of AChE measured in terms of Gibbs free binding energy. Of all the cerebrosides assessed, compound 6 exhibited strong interaction, followed by 15. This is the first report of molecular docking study on cerebrosides for AChE enzyme inhibition for treatment of Alzheimer’s disease. Nevertheless, detailed in vitro and in vivo, biochemical and molecular investigations are needed to bring them to useful form.

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