Molecular docking studies of flavonoids for their inhibition pattern against β-catenin and pharmacophore model generation from experimentally known flavonoids to fabricate more potent inhibitors for Wnt signaling pathway

Angiogenesis is defined as the formation of new blood vessels and is a key phenomenon manifested in a host of cancers during which tyrosine kinases play a crucial role. Vascular endothelial growth factor receptor-2 (VEGFR-2) is pivotal in cancer angiogenesis, which warrants the urgency of discovering new anti-angiogenic inhibitors that target the signalling pathways. To obtain this objective, a structure-based pharmacophore model was built from the drug target VEGFR-2 (PDB code: 4AG8), complexed with axitinib and was subsequently validated and employed as a 3D query to retrieve the candidate compounds with the key inhibitory features. The model was escalated to molecular docking studies resulting in seven candidate compounds. The molecular docking studies revealed that the seven compounds displayed a higher dock score than the reference-cocrystallised compound. The GROningen MAchine for Chemical Simulations (GROMACS) package guided molecular dynamics (MD) results determined their binding mode and affirmed stable root mean square deviation. Furthermore, these compounds have preserved their key interactions with the residues Glu885, Glu917, Cys919 and Asp1046. The obtained findings deem that the seven compounds could act as novel anti-angiogenic inhibitors and may further assist as the prototype in designing and developing new inhibitors.

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Quantitative structure-activity relationship and molecular docking studies on human proteasome inhibitors for anticancer activity targeting NF-κB signaling pathway

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2019.1666743 ◽

2019 ◽

Vol 38 (12) ◽

pp. 3621-3632

Author(s):

Deepika Yadav ◽

Bhartendu Nath Mishra ◽

Feroz Khan

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Signaling Pathway ◽

Proteasome Inhibitors ◽

Quantitative Structure Activity Relationship ◽

Docking Studies ◽

Activity Relationship ◽

Quantitative Structure ◽

Molecular Docking Studies ◽

Structure Activity

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Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus

Advances in Bioinformatics ◽

10.1155/2014/903246 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Pawan Kaushik ◽

Sukhbir Lal Khokra ◽

A. C. Rana ◽

Dhirender Kaushik

Keyword(s):

Molecular Docking ◽

Aldose Reductase ◽

Pharmacophore Model ◽

Docking Studies ◽

Antidiabetic Activity ◽

Bioactive Constituents ◽

Active Constituent ◽

Pinus Roxburghii ◽

Molecular Docking Studies ◽

Active Target

The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin receptor (IR) with help of docking software Molegro virtual docker (MVD). From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

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Pharmacophore model prediction, 3D-QSAR and molecular docking studies on vinyl sulfones targeting Nrf2-mediated gene transcription intended for anti-Parkinson drug design

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2015.1077343 ◽

2015 ◽

Vol 34 (6) ◽

pp. 1282-1297 ◽

Cited By ~ 21

Author(s):

Mohd Athar ◽

Mohsin Yousuf Lone ◽

Vijay M. Khedkar ◽

Prakash Chandra Jha

Keyword(s):

Molecular Docking ◽

Drug Design ◽

Gene Transcription ◽

Model Prediction ◽

Pharmacophore Model ◽

3D Qsar ◽

Docking Studies ◽

Molecular Docking Studies

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Bioactive compound 1,8-Cineole selectively induces G2/M arrest in A431 cells through the upregulation of the p53 signaling pathway and molecular docking studies

Phytomedicine ◽

10.1016/j.phymed.2018.04.007 ◽

2018 ◽

Vol 46 ◽

pp. 57-68 ◽

Cited By ~ 10

Author(s):

Sowndarya Sampath ◽

Sangeetha Subramani ◽

Sridevi Janardhanam ◽

Preethi Subramani ◽

Arun Yuvaraj ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Bioactive Compound ◽

Docking Studies ◽

A431 Cells ◽

Molecular Docking Studies ◽

P53 Signaling ◽

P53 Signaling Pathway

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Molecular docking studies for Vitex negundo (L) leaf extract compounds against Wnt- signaling proteins towards the treatment of colon cancer

Chemical Data Collections ◽

10.1016/j.cdc.2022.100829 ◽

2022 ◽

pp. 100829

Author(s):

Kuruvalli Gouthami ◽

V. Veeraraghavan ◽

L Lavanya ◽

C.N. Prashantha

Keyword(s):

Colon Cancer ◽

Molecular Docking ◽

Wnt Signaling ◽

Leaf Extract ◽

Docking Studies ◽

Signaling Proteins ◽

Vitex Negundo ◽

Molecular Docking Studies

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

Natural Product Communications ◽

10.1177/1934578x20978025 ◽

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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