scholarly journals Evaluation of the Inhibitory Activities of Ferula gummosa Bioactive Compounds against the Druggable Targets of SARS-CoV-2: Molecular Docking Simulation

2021 ◽  
Vol 12 (5) ◽  
pp. 6382-6392
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Simulation ◽  
Large Family ◽  
Viral Disease ◽  
Valuable Resource ◽  
Molecular Docking Simulation ◽  
Natural Components ◽  
Inhibitory Activities ◽  
Druggable Targets

SARS-CoV-2, an infectious disease caused by a novel strain that belongs to a large family of coronaviruses, has emerged as a global health threat. This viral disease affects the epithelial cells of the respiratory system and eventually leads to pneumonia. Using medicine derived from natural and safe herbs could be an alternative way of preventing or even treating severe respiratory disorders. This research has been conducted to evaluate the anti-inflammatory potential of Ferula gummosa Boiss. in preventing Covid-19. Molecular docking simulation was performed on the 18 components of Ferula gummosa against known active binding sites of SARS-CoV-2. The results revealed that these compounds inhibited the vital proteins of SARS-CoV-2, including 6LU7, 6EX1, 6W9C, and 6M71. According to the docking scores (DS) and inhibition constants (Ki), the most potent anti-coronavirus activity is expressed in the order: Δ-Cadinen > β-eudesmol > Bulnesol. The docking results revealed that the natural components of Ferula gummosa, mainly Δ-Cadinene, could be considered a valuable resource for preventing the infection of SARS-CoV-2.

Binding Investigation of Integrin αvβ3 With Its Inhibitors by SPR Technology and Molecular Docking Simulation

2010 ◽  
Vol 15 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Yaqin Liu ◽  
Yuanjiang Pan ◽  
Yuhong Xu
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Structural Model ◽  
Docking Simulation ◽  
Integrin Αvβ3 ◽  
Equilibrium Dissociation Constant ◽  
Molecular Docking Simulation ◽  
Spr Biosensor ◽  
Inhibitor Discovery ◽  
Equilibrium Dissociation

Integrins play critical roles in the process of angiogenesis and are attractive targets for anticancer therapies. It is desirable to develop new types of small-molecule inhibitors of integrin. Herein, the binding features of several inhibitors to integrin αvβ3 have been studied by surface plasmon resonance (SPR) biosensor technology and molecular docking analyses. The SPR results indicated that the equilibrium dissociation constant (KD) values are evaluated for the inhibitors and showed that the KD value of cyclopeptide c-Lys is much lower than the reference molecule. In addition, the 3D structural model of integrin αvβ3 was generated according to the crystal structure of the integrin αvβ3 complex, and the molecular docking simulation analyses revealed that the predicted binding sites for the most active cyclopeptide c-Lys were consistent with the reported structure. These results thus implied that cyclopeptide c-Lys could be developed as a novel inhibitor for integrin αvβ3. The current work has potential for application in structure-based integrin αvβ3 inhibitor discovery.

scholarly journals Molecular docking-simulation edge assessment of potential and less-toxic ‘anti- HIV-drug and phyto-flavonoid’ combination against COVID-19

2020 ◽  
Author(s):  
Shasank S. Swain ◽  
Satya R. Singh ◽  
Alaka Sahoo ◽  
Tahziba Hussain ◽  
Sanghamitra Pati
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
Docking Study ◽  
Viral Disease ◽  
Hiv Protease ◽  
Dynamics Simulation ◽  
Genome Replication ◽  
Molecular Docking Simulation ◽  
Docking Score ◽  
Anti Hiv

Abstract The emergence of the pandemic coronavirus-2019 (COVID-19) disease by the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) or 2019-novel coronavirus-2019 (2019- nCoV-2019) has created a disease-ridden environment for the entire human community, globally. However, no potent prophylactic therapy is available to control the deadly emerged viral disease. Repurposing of existing antiviral, antiinflammatory, antimalarial drugs is the only option against SARS-CoV-2. But without any clinical evidence, the recommended dose and expected side effects are under debate. As an alternative solution, we proposed a newer hypothesis using the selective, potent anti-HIV drugs and flavonoid class of phytochemicals in combination to balance the potency and toxicity during combat against SARS-CoV-2. Primarily, ten anti-HIV protease inhibitor drugs with ten phyto-flavonoids are selected as ligands for docking study against the putative target, the main protease (Mpro) of SARS-CoV-2 (PDB ID: 6Y2E), as an essential enzyme in viral genome replication. According to molecular docking and drug-ability scores of each ligand, the anti-HIV drug, the darunavir (with a docking score, -10.25 kcal/mol and drug-likeness rating, 0.60) and the quercetin-3-rhamnoside (with a docking score, -10.90 kcal/mol and drug-likeness rating, 0.82), were selected for further analysis in the mixture. Later, the interchanged mutual docking analysis suggested that ‘darunavir-quercetin-3- rhamnoside’ was the most potent and less toxic drug chemical-cocktail/ formulation against SARS-CoV-2-Mpro. Additionally, molecular dynamics simulation, predicted toxicity and pharmacokinetics profiles also support to the hypothesized formulation; mainly, eight strong H- bond interactions were found against SARS-CoV-2-Mpro. Thus, projected molecular docking- simulation based active and lesser toxic ‘anti-HIV-drug-phyto-flavonoid’ therapy could be promoted against SARS-CoV-2.

scholarly journals Kinase Inhibitory Activities and Molecular Docking of a Novel Series of Anticancer Pyrazole Derivatives

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3074 ◽  
Author(s):  
Eman Nossier ◽  
Somaia Abd El-Karim ◽  
Nagy Khalifa ◽  
Ali El-Sayed ◽  
Emad Hassan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Simulation ◽  
Braf V600e ◽  
Kinase Assay ◽  
Assay Method ◽  
Molecular Docking Simulation ◽  
Hct 116 ◽  
Mcf 7

A series of novel 1,3,4-triarylpyrazoles containing different heterocycles has been prepared, characterized and screened for their in vitro antiproliferative activity against HePG-2, MCF-7, PC-3, A-549 and HCT-116 cancer cell lines. The biological results revealed that compound 6 showed the highest anticancer activity so it was subjected to a kinase assay study where it reduced the activity of several protein kinases including AKT1, AKT2, BRAF V600E, EGFR, p38α and PDGFRβ at 100 μM using the radiometric or ADP-Glo assay method. Molecular docking simulation supported the initial kinase assay and suggested a common mode of interaction at the ATP-binding sites of these kinases, which demonstrates that compound 6 is a potential agent for cancer therapy deserving further research.

Design, Molecular docking, Synthesis and Biological evaluation of 5, 7 dimethyl pyrido(2, 3-d)pyrimidin-4-one and 4,5 dihydro pyrazolo (3, 4-d) pyrimidines for cytotoxic activity

2021 ◽  
pp. 3029-3038
Author(s):  
M. Sathish Kumar ◽  
M. Vijey Aanandhi
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Hep G2 ◽  
Molecular Docking Simulation ◽  
Hela Cell Lines ◽  
Benzene Diazonium ◽  
Synthesis And Biological Evaluation ◽  
Mcf 7

The fused pyrimidine derivatives are potent tyrosine kinase and thymidylate synthase inhibitors. The compound 3-(4-sulphonyl amino)-2-methyl thio-6-phenyl azo-5, 7-dimethyl pyrido(2,3-d)pyrimidin-4-one was synthesized from Ethyl 2-amino-4,6-dimethylpyridine-3-carboxylate, benzene diazonium chloride, benzene sulphonyl amino isothiocyanate in subsequent reactions. 1-(1, 3-benzothiazol-2-yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidines were synthesized from 1, 3-benzothiazole, 2-thiol, Hydrazine Hydrate, 2-hydrazinyl-1, 3-benzothiazole and aldehydes in subsequent reactions. Twenty-five derivatives pyrimidine scaffolds were designed and performed molecular docking studies for the ability to inhibit the target protein using molecular docking simulation, selective compounds were synthesized and characterized by spectral methods. All the synthesized compounds evaluated for their antioxidant activity and MTT assay exhibited compounds 13c, 13e and 14d can be potential anticancer candidates against MCF-7, Hep G2 and Hela cell lines respectively. Based on all the studies conclude that good agreement was observed between the top-ranked docking scores and top experimental inhibitors when compared with standards ascorbic acid and imatinib. Hence, the compounds could be considered as new anticancer hits for further lead optimization.

scholarly journals Discovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer

2020 ◽  
Vol 10 (1) ◽  
pp. 4929-4933
Keyword(s):  
Molecular Docking ◽  
Therapeutic Strategy ◽  
Docking Simulation ◽  
Drug Candidate ◽  
Synthetic Compounds ◽  
Molecular Docking Simulation ◽  
Docking Simulations ◽  
Lipinski’S Rule ◽  
Mercaptosuccinic Acid ◽  
Significant Public Health

As one of the most complex diseases in the world, cancer continues as one of the significant public health problems. It was recorded by 2014 that cancer caused 1,551,000 death in Indonesia. One type of programmed cell death (PCD) that played a role in cancer cell treatment is Ferroptosis. Ferroptosis is PCD on iron and characterized by the inactivation of glutathione-dependent peroxidase (GPx4). In this research, a new therapeutic strategy for cancer was developed through the computational approach on synthetic compounds to discover its potential as an inhibitor of GPx4. About 688 compounds derivative from mercaptosuccinic acid acquired from the Zinc15 database. These compounds screened through the Lipinski’s Rule of Three and pharmacological prediction to eliminate ligands with undesired molecular properties. After that, the ligands underwent both rigid and flexible molecular docking simulations to predict their inhibition activity toward GPx4. From molecular docking simulation, (2S)-2-[(Z)-3-phenylprop-2-enyl]sulfanylbutanedioic acid show favorable characteristics as a drug candidate.

PTP1B inhibitors from Selaginella tamariscina (Beauv.) Spring and their kinetic properties and molecular docking simulation

2017 ◽  
Vol 72 ◽  
pp. 273-281 ◽  
Author(s):  
Duc Dat Le ◽  
Duc Hung Nguyen ◽  
Bing Tian Zhao ◽  
Su Hui Seong ◽  
Jae Sue Choi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
Kinetic Properties ◽  
Molecular Docking Simulation ◽  
Selaginella Tamariscina ◽  
Ptp1b Inhibitors

scholarly journals Mechanisms of Compound Kushen Injection for the Treatment of Lung Cancer Based on Network Pharmacology

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Ziqi Meng ◽  
Xinkui Liu ◽  
Jiarui Wu ◽  
Wei Zhou ◽  
Kaihuan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Small Cell Lung Cancer ◽  
Docking Simulation ◽  
Small Cell ◽  
Network Pharmacology ◽  
Small Cell Lung ◽  
Molecular Docking Simulation ◽  
Target Network ◽  
Compound Kushen Injection

Background. Compound Kushen Injection (CKI) is a Chinese patent drug that shows good efficacy in treating lung cancer (LC). However, its underlying mechanisms need to be further clarified.Methods. In this study, we adopted a network pharmacology method to gather compounds, predict targets, construct networks, and analyze biological functions and pathways. Moreover, molecular docking simulation was employed to assess the binding potential of selected target-compound pairs.Results. Four networks were established, including the compound-putative target network, protein-protein interaction (PPI) network of LC targets, compound-LC target network, and herb-compound-target-pathway network. Network analysis showed that 8 targets (CHRNA3, DRD2, PRKCA, CDK1, CDK2, CHRNA5, MMP1, and MMP9) may be the therapeutic targets of CKI in LC. In addition, molecular docking simulation indicated that CHRNA3, DRD2, PRKCA, CDK1, CDK2, MMP1, and MMP9 had good binding activity with the corresponding compounds. Furthermore, enrichment analysis indicated that CKI might exert a therapeutic role in LC by regulating some important pathways, namely, pathways in cancer, proteoglycans in cancer, PI3K-Akt signaling pathway, non-small-cell lung cancer, and small cell lung cancer.Conclusions. This study validated and predicted the mechanism of CKI in treating LC. Additionally, this study provides a good foundation for further experimental studies and promotes the reasonable application of CKI in the clinical treatment of LC.

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