scholarly journals The structural diversity of ginsenosides affects their cholinesterase inhibitory potential

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Eda Özturan Özer ◽  
Oya Unsal Tan ◽  
Suna Turkoglu
Keyword(s):  
Molecular Docking ◽  
Enzyme Inhibitor ◽  
Direct Interaction ◽  
Structural Diversity ◽  
Docking Studies ◽  
Catalytic Triad ◽  
Active Components ◽  
Molecular Docking Studies ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

AbstractBackground/ObjectiveGinsenosides, the major active components of the ginseng, are known to have various effects on nervous systems. The present study aimed to clarify the inhibition potentials of ginsenosides Rb1, Rc, Re and Rg1 on acetylcholinesterase (AChE) and butrylcholinesterase (BChE) activities, and to evaluate the underlying mechanisms of inhibitions provided by protein-ligand interactions considering their probable candidates of prodrug.Materials and methodsThe inhibitory mechanisms of ginsenosides related with their structural diversity were analyzed kinetically and protein-ligand interactions for both enzymes were evaluated with most potent ginsenosides, by molecular docking studies.ResultsGinsenosides Re and Rg1, with sugar moieties attached to the C-6 and C-20 positions of core structure were found to possess the most powerful inhibitory effect on AChE and BChE activities. Molecular docking studies have been confirmed by kinetic studies. Ginsenosides having a direct interaction with amino acid residues belonging to the catalytic triad revealed the most powerful inhibition with lowest enzyme-inhibitor dissociation constant (Ki) values.ConclusionsGinsenosides Re and Rg1, either alone or in a specific combination, may provide beneficial effects on neurodegenerative pathologies in therapeutic terms.

Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 233-247
Author(s):  
Krishna A. Gajjar ◽  
Anuradha K. Gajjar
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Docking Studies ◽  
Structural Motif ◽  
Roc Curve Analysis ◽  
Ligand Complex ◽  
Discovery Studio ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Pharmacophore Models

Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the molecular docking studies; using SYBYL-X 1.2 software. Results and Conclusion: Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted phenyl propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biological protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study.

Solvent induced mononuclear and dinuclear mixed ligand Cu(ii) complex: structural diversity, supramolecular packing polymorphism and molecular docking studies

2020 ◽  
Vol 44 (41) ◽  
pp. 18048-18068
Author(s):  
Mahesha ◽  
M. K. Hema ◽  
C. S. Karthik ◽  
K. J. Pampa ◽  
P. Mallu ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Molecular Docking ◽  
Structural Diversity ◽  
Docking Studies ◽  
Mixed Ligand ◽  
Molecular Docking Studies ◽  
Complex Structural

Phenolate bridged dinuclear and solvent induced mononuclear supramolecular isomers of Cu(ii) complex have been reported to explore the structural diversity and their antibacterial activity supported by molecular docking studies.

scholarly journals Structure Based Design and Molecular Docking Studies for Phosphorylated Tau Inhibitors in Alzheimer’s Disease

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 260 ◽  
Author(s):  
Jangampalli Pradeepkiran ◽  
P. Reddy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Drug Target ◽  
Docking Studies ◽  
Toxicity Tests ◽  
Phosphorylated Tau ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Alternative Drug

The purpose of our study is to identify phosphorylated tau (p-tau) inhibitors. P-tau has recently received great interest as a potential drug target in Alzheimer’s disease (AD). The continuous failure of Aβ-targeted therapeutics recommends an alternative drug target to treat AD. There is increasing evidence and growing awareness of tau, which plays a central role in AD pathophysiology, including tangles formation, abnormal activation of phosphatases/kinases, leading p-tau aggregation in AD neurons. In the present study, we performed computational pharmacophore models, molecular docking, and simulation studies for p-tau in order to identify hyperphosphorylated sites. We found multiple serine sites that altered the R1/R2 repeats flanking sequences in the tau protein, affecting the microtubule binding ability of tau. The ligand molecules exhibited the p-O ester scaffolds with inhibitory and/or blocking actions against serine residues of p-tau. Our molecular docking results revealed five ligands that showed high docking scores and optimal protein-ligand interactions of p-tau. These five ligands showed the best pharmacokinetic and physicochemical properties, including good absorption, distribution, metabolism, and excretion (ADME) and admetSAR toxicity tests. The p-tau pharmacophore based drug discovery models provide the comprehensive and rapid drug interventions in AD, and tauopathies are expected to be the prospective future therapeutic approach in AD.

scholarly journals Mechanistic Validation of an Ergogenic T. arjuna Standardized Extract (Oxyjun®) Using a Molecular Docking Approach

2021 ◽  
pp. 54-63
Author(s):  
Kavita Pandey ◽  
Gursimran Kaur Uppal ◽  
Ratna Upadhyay
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Terminalia Arjuna ◽  
Lipinski’S Rule ◽  
Protein Ligand Interactions ◽  
Potential Efficacy ◽  
Ligand Interactions ◽  
Docking Approach ◽  
Cardio Vascular ◽  
Botanical Extract

The bark of the tree Terminalia arjuna commonly referred as Arjuna is widely used in Ayurveda as a therapeutic agent for heart disease. More recently, a proprietary botanical extract of T. arjuna with tradename, Oxyjun®, demonstrated cardiotonic and ergogenic benefits for the first time in a younger and healthier population. However, the mechanism of action and biological actives of this novel sports ingredient were not clear. A molecular docking approach was adopted to understand the protein-ligand interactions and establish the most probable mechanism(s) of cardio vascular actions of the phytoconstituents of the T. arjuna standardized extract (TASE). Twenty-one phytochemicals (ligands) were chosen from Arjuna and their binding affinities against eight proteins serving cardiovascular functions (target proteins) were investigated. Autodock Vina was used to carry out the molecular docking studies. Potential efficacy in humans was assessed on the basis of ADMET properties and Lipinski’s Rule of 5. We found that arjunic acid, arjungenin, arjunetin, arjunglucoside1, chrysin, kaempferol, luteolin, rhamnetin and taxifolin demonstrated good docking scores and bioactivity.

scholarly journals Docking studies in targeting proteins involved in cardiovascular disorders using phytocompounds from Terminalia arjuna

2020 ◽  
Author(s):  
Vikas Kumar ◽  
Nitin Sharma ◽  
Anuradha Sourirajan ◽  
Prem Kumar Khosla ◽  
Kamal Dev
Keyword(s):  
Molecular Docking ◽  
3D Structure ◽  
Three Dimensional ◽  
Data Bank ◽  
Docking Studies ◽  
Terminalia Arjuna ◽  
Structure Based Drug Design ◽  
Lipinski’S Rule ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

AbstractTerminalia arjuna (Roxb.) Wight and Arnot (T. arjuna) commonly known as Arjuna has been known for its cardiotonic nature in heart failure, ischemic, cardiomyopathy, atherosclerosis, myocardium necrosis and also has been used in the treatment of different human disorders such as blood diseases, anaemia and viral diseases. Our focus has been on phytochemicals which do not exhibit any cytotoxicity and have significant cardioprotective activity. Since Protein-Ligand interactions play a key role in structure-based drug design, therefore with the help of molecular docking, we screened 19 phytochemicals present in T. arjuna and investigated their binding affinity against different cardiovascular target proteins. The three-dimensional (3D) structure of target cardiovascular proteins were retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 19 phytochemicals using Autodock vina. Molecular docking and drug-likeness studies were made using ADMET properties while Lipinski’s rule of five was performed for the phytochemicals to evaluate their cardio protective activity. Among all selected phytocompounds, arjunic acid, arjungenin, and terminic acid were found to fulfill all ADMET rules, drug likeness, and are less toxic in nature. Our studies, therefore revealed that these three phytochemicals from T. arjuna can be used as promising candidates for developing broad spectrum drugs against cardiovascular diseases.

scholarly journals Antibacterial, Antifungal Chalcone Derivatives as EGFR Inhibitors-Molecular Docking and ADMET Studies

2021 ◽  
pp. 387-396
Author(s):  
Hemalatha Sattu ◽  
Indira rani Nerella ◽  
Saritha Jyostna Tangeda
Keyword(s):  
Molecular Docking ◽  
Growth Factor Receptor ◽  
Docking Simulation ◽  
Docking Studies ◽  
Binding Energies ◽  
Receptor Protein ◽  
Molecular Docking Studies ◽  
Chalcone Derivatives ◽  
Ligand Interactions ◽  
Protein Environment

Aim: In our earlier research, we have synthesized series of substituted 1-(2, 5-dimethyl thiophene-3yl)-(4-substituted phenyl)-2-propene-1-one derivatives and evaluated them for their anti-bacterial and antifungal activity. In recent years, chalcone derivatives are proved for their varied pharmacological effects ranging from antimicrobial activity to anti-cancer effects. In this study, we have hypothesized the efficiency of our earlier synthesized anti-bacterial and antifungal chalcone derivatives for their potential inhibition of epidermal growth factor receptor protein (EGFR), through molecular docking studies. Methodology: Molecular docking simulation studies are performed using the Glide XP module of Schrodinger Suite and ligand binding energies are also calculated. Results: Molecular docking studies of the selected compounds against EGFR revealed docking scores ranging from -6.746 (compound 5) to -5.681 (compound 3) and also provided insight into binding conformations of the ligands in the EGFR protein environment. Additionally, molecular property and Absorption, Distribution, Metabolism, and Excretion (ADME) predictor analysis is also performed for the dataset ligands, which further provided the probable explanation for the binding potentials. Conclusion: Among all the tested dataset ligands, compound 5 has shown the highest dock score (-6.746) with better ADME profiles. Binding energies in the protein-ligand interactions explain how fit the ligand binds with the target protein. Molecular docking studies of these anti-bacterial, antifungal chalcone derivatives provided deeper insights in understanding the probable conformations of these tested ligands in the EGFR protein environment.

scholarly journals Network Pharmacology Integrated Molecular Docking Reveals the Anti-COVID-19 Mechanism of Xingnaojing Injection

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2097802
Author(s):  
Bing Yu ◽  
Xin-Ge Ke ◽  
Chong Yuan ◽  
Peng-Yu Chen ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Growth Factor Receptor ◽  
Docking Studies ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Active Components ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Xingnaojing Injection

In the process of fighting against COVID-19 in China, Xingnaojing injection has been recommended for its clinical treatment, but the information about its active components and mechanism is still lacking. Therefore, in this work, using network pharmacology and molecular docking, we studied the active components of Xingnaojing injection having anti-COVID-19 properties. Using the DL parameter, TCMSP and CNKI databases were used to screen the active components of the Xingnaojing injection. Then, the SwissTargetPrediction webserver was used to collect the corresponding gene targets, and the gene targets related to COVID-19 were searched in the Genecards database. The DAVID database was used to enrich the function of gene targets, and the KOBAS3.0 database for the annotation of related KEGG pathways. The “components–targets–pathways” network of Xingnaojing injection was constructed with Cytoscape 3.6.1 software. The protein–protein interaction networks were analyzed using the String database. Specific proteins, SARS-COV-2 3 Cl, ACE2, and the active components were imported into Discovery Studio 2016 Client for molecular docking studies. From the Xingnaojing injection, a total of 58 active components, including Divanillalaceton and Q27139023, were screened. These were linked to 53 gene targets including mitogen-activated protein kinase 1 (MAPK1), tumor necrosis factorTNF, epidermal growth factor receptor, MAPK3, and 196 signaling pathways related to COVID-19, such as apoptosis, C-type lectin receptor signaling pathway, and hypoxia-inducible factor 1 signaling pathway. Furthermore, molecular docking studies were performed to study potential binding between the key targets and selected active components. Xingnaojing injection exhibits anti-COVID-19 effects via multiple components, multiple targets, and multiple pathways. These results set a scientific basis for further elucidation of the anti-COVID-19 mechanism of Xingnaojing injection.

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