Structural insights into flavones as protein kinase CK2 inhibitors derived from a combined computational study

Lv, Min; Ma, Shuying; Tian, Yueli; Zhang, Xiaoyun; Zhai, Hong Lin; Lv, Wenjuan

doi:10.1039/c4ra10381e

Cited by 7 publications

(3 citation statements)

References 44 publications

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“…17 In recent years, many studies had indicated that computational approaches can timely provide very useful information and insights for drug development. [18][19][20] Such as predicting functions of proteins, 21 structural bioinformatics, 22 molecular docking, and predicting drug-target interaction [23][24][25] were widely welcome by science community. Quantitative structure-activity relationship (QSAR) method, as a powerful quantitative methodology, were proved to be one of the most promising and successful methods for rapidly predicting the biological activity and/or toxicity of chemicals.…”

Section: Introductionmentioning

confidence: 99%

Discovery of vascular endothelial growth factor receptor tyrosine kinase inhibitors by quantitative structure–activity relationships, molecular dynamics simulation and free energy calculation

et al. 2016

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Section: Introductionmentioning

confidence: 99%

Discovery of vascular endothelial growth factor receptor tyrosine kinase inhibitors by quantitative structure–activity relationships, molecular dynamics simulation and free energy calculation

et al. 2016

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“…Using molecular docking, key amino acids (Asp335, Tyr383, and Gln384) were identified owing to the docking of flexible ligand into rigid receptor. MD analysis can support these docking results through the fluidity of their complexes, or identify new key interactions [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

In Vitro and In Silico Insights into sEH Inhibitors with Amide-Scaffold from the Leaves of Capsicum chinense Jacq.

Kim

et al. 2018

Computational and Structural Biotechnology Journal

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Two compounds termed 1 and 2 were isolated from the leaves of Capsicum chinense using column chromatography. Their structures were identified as amide scaffolds by analyzing spectroscopic signals. Compounds 1 and 2 have been confirmed to be competitive soluble epoxide hydrolase (sEH) inhibitors that suppress the catalytic reaction of sEH in a dose-dependent manner in vitro. Molecular docking was used for analyzing two binding clusters of ligand and receptor. The results confirmed that the key amino acids interacting with the ligand were Asp335, Tyr383, and Gln384. On the basis of molecular dynamics, inhibitors 1 and 2 were noted to interact at a distance of 3.5 Å from Asp335, Tyr383, Leu408 and Tyr466, and Asp335, Tyr383, and Tyr466, respectively. These results highlight the potential of N-trans-coumaroyltyramine (1) and N-trans-feruloyltyramine (2) as sEH inhibitors.

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“…Molecular docking is an increasingly significant method in realizing the foundation of ligand-protein recognition. 17 To evaluate the potential interaction of the vitamins and XO at the atomic level, AutoDock 4.2 (Scripps, USA) under a simulation environment (298.15 K) was applied. XO is a homodimer, each monomer acts independently with a molybdenum (Mo) center, two [2Fe-2S] clusters and an FAD cofactor.…”

Section: In Silico Molecular Docking Studymentioning

confidence: 99%

The inhibitory kinetics and mechanism of dietary vitamins D₃and B₂on xanthine oxidase

et al. 2016

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Dietary guidelines to promote health are usually based on the patterns' prediction on disease risk of foods and nutrients. Overactivity of xanthine oxidase (XO) is the underlying cause of gout. Herein, the inhibitory kinetics and mechanism of dietary vitamins D3 and B2 on XO were investigated by multispectroscopic methods and a molecular modeling technique. The results showed that vitamin D3 competitively inhibited XO with an inhibition constant of 26.93 ± 0.42 μM by inserting into the active cavity of XO interacting with the surrounding amino acid residues through hydrogen bond and van der Waals forces. Vitamin D3 bound to XO thereby induced the structural compactness of XO which in turn hindered the binding of substrate xanthine to cause the inhibition on XO. Vitamin B2 exhibited a mixed-type inhibition by binding to the vicinity of the active cavity with an inhibition constant of 37.76 ± 0.87 μM through hydrophobic interactions and a feeble hydrogen bond, and it induced the unfolding of the XO structure and an increase of the flexible loops (β-turns and random coils) which might move to cover the active pocket and reduce the binding of the substrate xanthine, and then lead to a lower catalytic activity of the enzyme. In addition, vitamins D3 and B2 showed a synergistic effect on inhibiting the activity of XO in a certain range of concentration. These findings may provide new insights into the inhibitory mechanism of vitamins D3 and B2 on XO and functional research of the vitamins in the supplementary treatment of gout.

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Structural insights into flavones as protein kinase CK2 inhibitors derived from a combined computational study

Abstract: Binding conformation of flavone inhibitors to protein kinase CK2.

Cited by 7 publications

References 44 publications

Discovery of vascular endothelial growth factor receptor tyrosine kinase inhibitors by quantitative structure–activity relationships, molecular dynamics simulation and free energy calculation

Discovery of vascular endothelial growth factor receptor tyrosine kinase inhibitors by quantitative structure–activity relationships, molecular dynamics simulation and free energy calculation

In Vitro and In Silico Insights into sEH Inhibitors with Amide-Scaffold from the Leaves of Capsicum chinense Jacq.

The inhibitory kinetics and mechanism of dietary vitamins D₃and B₂on xanthine oxidase

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Structural insights into flavones as protein kinase CK2 inhibitors derived from a combined computational study

Abstract: Binding conformation of flavone inhibitors to protein kinase CK2.

Cited by 7 publications

References 44 publications

Discovery of vascular endothelial growth factor receptor tyrosine kinase inhibitors by quantitative structure–activity relationships, molecular dynamics simulation and free energy calculation

Discovery of vascular endothelial growth factor receptor tyrosine kinase inhibitors by quantitative structure–activity relationships, molecular dynamics simulation and free energy calculation

In Vitro and In Silico Insights into sEH Inhibitors with Amide-Scaffold from the Leaves of Capsicum chinense Jacq.

The inhibitory kinetics and mechanism of dietary vitamins D3and B2on xanthine oxidase

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The inhibitory kinetics and mechanism of dietary vitamins D₃and B₂on xanthine oxidase