C-methyl flavonoid from the leaves of Cleistocalyx conspersipunctatus:α-glucosidase inhibitory, molecular docking simulation and biosynthetic pathway

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.

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Discovery of a Highly Potent Tyrosinase Inhibitor, Luteolin 5-O-β-d-Glucopyranoside, Isolated from Cirsium japonicum var. maackii (Maxim.) Matsum., Korean Thistle: Kinetics and Computational Molecular Docking Simulation

ACS Omega ◽

10.1021/acsomega.8b02694 ◽

2018 ◽

Vol 3 (12) ◽

pp. 17236-17245 ◽

Cited By ~ 4

Author(s):

Aditi Wagle ◽

Su Hui Seong ◽

Eun-Ji Joung ◽

Hyeung-Rak Kim ◽

Hyun Ah Jung ◽

...

Keyword(s):

Molecular Docking ◽

Docking Simulation ◽

Tyrosinase Inhibitor ◽

Molecular Docking Simulation ◽

Cirsium Japonicum ◽

Computational Molecular Docking

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

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057109356207 ◽

2010 ◽

Vol 15 (2) ◽

pp. 131-137 ◽

Cited By ~ 14

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.

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

Biointerface Research in Applied Chemistry ◽

10.33263/briac101.929933 ◽

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.

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

Bioorganic Chemistry ◽

10.1016/j.bioorg.2017.05.001 ◽

2017 ◽

Vol 72 ◽

pp. 273-281 ◽

Cited By ~ 8

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

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/4637839 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 7

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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