scholarly journals Norditerpenoids with Selective Anti-Cholinesterase Activity from the Roots of Perovskia atriplicifolia Benth.

2020 ◽  
Vol 21 (12) ◽  
pp. 4475 ◽  
Author(s):  
Sylwester Ślusarczyk ◽  
F. Sezer Senol Deniz ◽  
Renata Abel ◽  
Łukasz Pecio ◽  
Horacio Pérez-Sánchez ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Medicinal Plant ◽  
Neurodegenerative Diseases ◽  
In Silico ◽  
Cholinesterase Activity ◽  
Treatment Strategies ◽  
Lead Compounds ◽  
Central Asian ◽  
Neurodegenerative Dementias ◽  
Anticholinesterase Properties

Inhibition of cholinesterases remains one of a few available treatment strategies for neurodegenerative dementias such as Alzheimer’s disease and related conditions. The current study was inspired by previous data on anticholinesterase properties of diterpenoids from Perovskia atriplicifolia and other Lamiaceae species. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by the three new natural compounds—(1R,15R)-1-acetoxycryptotanshinone (1), (1R)-1-acetoxytanshinone IIA (2), and (15R)-1-oxoaegyptinone A (3)—as well as, new for this genus, isograndifoliol (4) were assessed. Three of these compounds exhibited profound inhibition of butyrylcholinesterase (BChE) and much weaker inhibition of acetylcholinesterase (AChE). All compounds (1–4) selectively inhibited BChE (IC50 = 2.4, 7.9, 50.8, and 0.9 µM, respectively), whereas only compounds 3 and 4 moderately inhibited AChE (IC50 329.8 µM and 342.9 µM). Molecular docking and in silico toxicology prediction studies were also performed on the active compounds. Natural oxygenated norditerpenoids from the traditional Central Asian medicinal plant P. atriplicifolia are selective BChE inhibitors. Their high potential makes them useful candidate molecules for further investigation as lead compounds in the development of a natural drug against dementia caused by neurodegenerative diseases.

scholarly journals In-silico screening of active molecules from medicinal plant resources for controlling SARS-CoV-2 infection

2020 ◽  
Vol 6 (3) ◽  
pp. 149-153
Author(s):  
Rajdeep Ghosh ◽  
◽  
Satadru Palbag ◽  
Debasish Ghosh ◽  
◽  
...  
Keyword(s):  
Molecular Docking ◽  
Medicinal Plant ◽  
In Silico ◽  
Human Population ◽  
Treatment Strategies ◽  
Viral Proteins ◽  
Spike Protein ◽  
Plant Resources ◽  
In Silico Screening ◽  
Life Threatening

The entire human population is under treat of SARS-Cov-2 virus causing life threatening complicacies. Three proteins namely papain-like protease (PLpro), 3C-like protease (3CLpro) and spike protein isolated from the virus have been targeted for formulating the antiviral medicament. Ayurvedic medicinal plants with established antiviral efficacy are great choice to design immediate treatment strategies in this trying time. Here, 9 active molecules from ayurvedic medicinal plant resources were selected, out of which only 6 have screened through ADME analysis and molecular docking was performed with the three viral proteins to understand their antiviral performances in in silico model. Outcome of this study will surely open up a floodgate of thousand new possibilities in exploiting the existing natural herbs in COVID 19 treatments.

In-silico prediction of the beta carboline alkaloids Harmine and Harmaline as potent drug candidates for the treatment of Parkinson’s disease

2020 ◽  
Vol 19 ◽  
Author(s):  
Rumpa Banerjee ◽  
Mukesh Kumar ◽  
Isha Gaurav ◽  
Sudha Thakur ◽  
Abhimanyu Thakur ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Dopamine Receptors ◽  
Binding Affinity ◽  
In Silico ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Toxicity Profile ◽  
Drug Candidates

Background:: Parkinson’s disease (PD) is a progressive neurodegenerative disease manifested by core symptoms of loss of motor control and postural instability. Loss of dopaminergic neurons is the cause of PD, thus enhancing dopamine level by pharmacological treatment is one of the key treatment strategies for PD. However, limitations of current treatment strategies open the possibility of novel drug candidates for the treatment of PD. Objective:: To investigate the anti-PD potential of Harmine and Harmaline. We aim to evaluate the therapeutic potential of Harmine and Harmaline by in-silico approaches; molecular docking, pharmacokinetic and Prediction of Activity Spectra for Substances (PASS) analysis were used for evaluating the therapeutic potential of Harmine and Harmaline and standard drug levodopa (L-DOPA). Methods:: Auto dock vina was used for molecular docking of all three compounds against D2- and D3- dopamine receptors. The pharmacokinetics (PKs) and toxicity profile were predicted by pkCSM and the pharmacological activity was predicted by PASS analysis. Results:: Molecular docking showed a higher binding affinity of Harmine and Harmaline as compared to L-DOPA, and these results were supported by in-silico pharmacokinetic and toxicity profiling. Moreover, PASS analysis showed anti-PD activi-ty of Harmine and Harmaline. Conclusion:: Harmine and Harmaline exhibit higher binding affinity towards D2- and D3- dopamine receptors compared to L-DOPA, and PKs and toxicity profile support their potential as drug candidates for PD therapy.

scholarly journals Computational Studies Towards Identification of Lead Herbal Compounds of Medicinal Importance for Development of Nutraceutical Against COVID-19

2020 ◽  
Author(s):  
Amit Kumar Srivastav ◽  
Sanjeev Kumar Gupta ◽  
Umesh Kumar
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Md Simulation ◽  
Low Cost ◽  
Computational Studies ◽  
Ramachandran Plot ◽  
Lead Compounds ◽  
Cryo Electron Microscopy ◽  
Main Protease ◽  
In Silico Study

In the present study, we have performed the in-silico study of SARS-CoV-2 structure with different herbal compounds of medicinal importance. We selected four <a>viral key proteins of SARS-CoV-2 </a>structure i.e ACE-2 Receptor, Main Protease (Mpro), APO Form, Cryo- electron microscopy structure for the Molecular docking followed by the molecular dynamic simulation. Using this simple in silico approach based on the molecular docking and <a>MD simulation </a>of protein and phytochemicals, we have identified potential lead candidates for the development of low cost nutraceuticals, which can be used against SARS-CoV-2 virus. Our analysis suggested that phytochemicals obtained from <i>Phyllanthus emblica</i> and <i>Azadirachta indica</i> have the highest potential to bind with ACE2 receptor or main protease of SARS-CoV-2, inhibiting the protease enzymatic activity. The lead compounds of herbal origin were docked and simulated on viral key proteins of SARS-CoV-2 structure to evaluate the binding affinity of these phytochemicals along with the type of interaction and its stability in terms of <a>RMSD</a> and <a>Ramachandran plot</a>. Further, these results were also verified by drug likeness properties by using SwissADME software. Overall, our results suggest that out of 14 herbal compounds, Nimbolide and Withaferin-A has great potential to be developed as low-cost nutraceuticals against SARS-CoV-2 virus, which is the need of hour.

scholarly journals Computational Studies Applied to Flavonoids against Alzheimer’s and Parkinson’s Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-21 ◽  
Author(s):  
Alex France M. Monteiro ◽  
Jéssika De O. Viana ◽  
Anuraj Nayarisseri ◽  
Ernestine N. Zondegoumba ◽  
Francisco Jaime B. Mendonça Junior ◽  
...  
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Neurodegenerative Diseases ◽  
In Silico ◽  
Docking Studies ◽  
Binding Energies ◽  
Computational Studies ◽  
Epicatechin Gallate ◽  
Drug Candidates ◽  
Parkinson’S Diseases

Neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, are understood as occurring through genetic, cellular, and multifactor pathophysiological mechanisms. Several natural products such as flavonoids have been reported in the literature for having the capacity to cross the blood-brain barrier and slow the progression of such diseases. The present article reports on in silico enzymatic target studies and natural products as inhibitors for the treatment of Parkinson’s and Alzheimer’s diseases. In this study we evaluated 39 flavonoids using prediction of molecular properties and in silico docking studies, while comparing against 7 standard reference compounds: 4 for Parkinson’s and 3 for Alzheimer’s. Osiris analysis revealed that most of the flavonoids presented no toxicity and good absorption parameters. The Parkinson’s docking results using selected flavonoids as compared to the standards with four proteins revealed similar binding energies, indicating that the compounds 8-prenylnaringenin, europinidin, epicatechin gallate, homoeriodictyol, capensinidin, and rosinidin are potential leads with the necessary pharmacological and structural properties to be drug candidates. The Alzheimer’s docking results suggested that seven of the 39 flavonoids studied, being those with the best molecular docking results, presenting no toxicity risks, and having good absorption rates (8-prenylnaringenin, europinidin, epicatechin gallate, homoeriodictyol, aspalathin, butin, and norartocarpetin) for the targets analyzed, are the flavonoids which possess the most adequate pharmacological profiles.

scholarly journals Computational Studies Towards Identification of Lead Herbal Compounds of Medicinal Importance for Development of Nutraceutical Against COVID-19

2020 ◽  
Author(s):  
Amit Kumar Srivastav ◽  
Sanjeev Kumar Gupta ◽  
Umesh Kumar
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Md Simulation ◽  
Low Cost ◽  
Computational Studies ◽  
Ramachandran Plot ◽  
Lead Compounds ◽  
Cryo Electron Microscopy ◽  
Main Protease ◽  
In Silico Study

In the present study, we have performed the in-silico study of SARS-CoV-2 structure with different herbal compounds of medicinal importance. We selected four <a>viral key proteins of SARS-CoV-2 </a>structure i.e ACE-2 Receptor, Main Protease (Mpro), APO Form, Cryo- electron microscopy structure for the Molecular docking followed by the molecular dynamic simulation. Using this simple in silico approach based on the molecular docking and <a>MD simulation </a>of protein and phytochemicals, we have identified potential lead candidates for the development of low cost nutraceuticals, which can be used against SARS-CoV-2 virus. Our analysis suggested that phytochemicals obtained from <i>Phyllanthus emblica</i> and <i>Azadirachta indica</i> have the highest potential to bind with ACE2 receptor or main protease of SARS-CoV-2, inhibiting the protease enzymatic activity. The lead compounds of herbal origin were docked and simulated on viral key proteins of SARS-CoV-2 structure to evaluate the binding affinity of these phytochemicals along with the type of interaction and its stability in terms of <a>RMSD</a> and <a>Ramachandran plot</a>. Further, these results were also verified by drug likeness properties by using SwissADME software. Overall, our results suggest that out of 14 herbal compounds, Nimbolide and Withaferin-A has great potential to be developed as low-cost nutraceuticals against SARS-CoV-2 virus, which is the need of hour.

scholarly journals Potential Anti-Cancer Flavonoids Isolated From Caesalpinia bonduc Young Twigs and Leaves: Molecular Docking and In Silico Studies

2019 ◽  
Vol 13 ◽  
pp. 117793221882137 ◽  
Author(s):  
Franklyn Nonso Iheagwam ◽  
Olubanke Olujoke Ogunlana ◽  
Oluseyi Ebenezer Ogunlana ◽  
Itunuoluwa Isewon ◽  
Jelili Oyelade
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Strong Interactions ◽  
Cytotoxic Activities ◽  
Target Proteins ◽  
Lead Compounds ◽  
In Silico Studies ◽  
Anti Cancer ◽  
Therapeutic Molecules ◽  
Endothelial Growth Factor

Tyrosine kinase (TK), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are important cancer therapeutic target proteins. Based on reported anti-cancer and cytotoxic activities of Caesalpinia bonduc, this study isolated phytochemicals from young twigs and leaves of C bonduc and identified the interaction between them and cancer target proteins (TK, VEGF, and MMP) in silico. AutoDock Vina, iGEMDOCK, and analysis of pharmacokinetic and pharmacodynamic properties of the isolated bioactives as therapeutic molecules were performed. Seven phytochemicals (7-hydroxy-4′-methoxy-3,11-dehydrohomoisoflavanone, 4,4′-dihydroxy-2’-methoxy-chalcone, 7,4′-dihydroxy-3,11-dehydrohomoisoflavanone, luteolin, quercetin-3-methyl, kaempferol-3-O-β-d-xylopyranoside and kaempferol-3-O-α-l-rhamnopyranosyl-(1 → 2)-β-D-xylopyranoside) were isolated. Molecular docking analysis showed that the phytochemicals displayed strong interactions with the proteins compared with their respective drug inhibitors. Pharmacokinetic and pharmacodynamic properties of the compounds were promising suggesting that they can be developed as putative lead compounds for developing new anti-cancer drugs.

scholarly journals In-silico design of novel myocilin inhibitors for glaucoma therapy

2017 ◽  
Vol 16 (10) ◽  
pp. 2527-2533
Author(s):  
Min Tang ◽  
Yang Fu ◽  
Ying Fan ◽  
Ming-Shui Fu ◽  
Zhi Zheng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Binding Energies ◽  
Computational Approaches ◽  
Screening Technique ◽  
Lead Compounds ◽  
Potent Inhibition ◽  
Pharmacokinetic Properties ◽  
Molecular Libraries

Purpose: To explore newer computational approaches in the design of novel myocilin inhibitors for the treatment of glaucoma.Methods: An in-silico virtual screening technique based on simulation of molecular docking was utilised to design a novel myocilin inhibitors for the treatment of  glaucoma. The designed novel molecules were theoretically evaluated to predict their pharmacokinetic properties and toxic effects. Lead molecules were screened out in virtual screening technique on the basis of low binding energies obtained in AutoDock based molecular docking simulation.Results: Out of ten top lead compounds screened, ZINC01729523 and ZINC04692015 were promising, having shown potent inhibition of myocilin, good pharmacokinetic properties and absence of any toxic effects.Conclusion: In-silico virtual screening of molecular libraries containing a large number of ligands is very useful for short-listing of potential lead molecules for further structure-based discovery of antiglaucoma-drugs.Keywords: Glaucoma, Myocilin, Docking, Virtual-screening, Autodock, Ligand, Drug design

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