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Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods

The Mitogen-Activated Protein Kinase (MAPK) signaling pathway plays an important role in cancer cell proliferation and survival. MAPKs’ protein kinases MEK1/2 serve as important targets in drug designing against cancer. The natural compounds’ flavonoids are known for their anticancer activity. This...

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Autores principales: AlZahrani, Wejdan M., AlGhamdi, Shareefa A., Zughaibi, Torki A., Rehan, Mohd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876294/
https://www.ncbi.nlm.nih.gov/pubmed/35215307
http://dx.doi.org/10.3390/ph15020195
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author AlZahrani, Wejdan M.
AlGhamdi, Shareefa A.
Zughaibi, Torki A.
Rehan, Mohd
author_facet AlZahrani, Wejdan M.
AlGhamdi, Shareefa A.
Zughaibi, Torki A.
Rehan, Mohd
author_sort AlZahrani, Wejdan M.
collection PubMed
description The Mitogen-Activated Protein Kinase (MAPK) signaling pathway plays an important role in cancer cell proliferation and survival. MAPKs’ protein kinases MEK1/2 serve as important targets in drug designing against cancer. The natural compounds’ flavonoids are known for their anticancer activity. This study aims to explore flavonoids for their inhibition ability, targeting MEK1 using virtual screening, molecular docking, ADMET prediction, and molecular dynamics (MD) simulations. Flavonoids (n = 1289) were virtually screened using molecular docking and have revealed possible inhibitors of MEK1. The top five scoring flavonoids based on binding affinity (highest score for MEK1 is −10.8 kcal/mol) have been selected for further protein–ligand interaction analysis. Lipinski’s rule (drug-likeness) and absorption, distribution, metabolism, excretion, and toxicity predictions were followed to find a good balance of potency. The selected flavonoids of MEK1 have been refined with 30 (ns) molecular dynamics (MD) simulation. The five selected flavonoids are strongly suggested to be promising potent inhibitors for drug development as anticancer therapeutics of the therapeutic target MEK1.
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spelling pubmed-88762942022-02-26 Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods AlZahrani, Wejdan M. AlGhamdi, Shareefa A. Zughaibi, Torki A. Rehan, Mohd Pharmaceuticals (Basel) Article The Mitogen-Activated Protein Kinase (MAPK) signaling pathway plays an important role in cancer cell proliferation and survival. MAPKs’ protein kinases MEK1/2 serve as important targets in drug designing against cancer. The natural compounds’ flavonoids are known for their anticancer activity. This study aims to explore flavonoids for their inhibition ability, targeting MEK1 using virtual screening, molecular docking, ADMET prediction, and molecular dynamics (MD) simulations. Flavonoids (n = 1289) were virtually screened using molecular docking and have revealed possible inhibitors of MEK1. The top five scoring flavonoids based on binding affinity (highest score for MEK1 is −10.8 kcal/mol) have been selected for further protein–ligand interaction analysis. Lipinski’s rule (drug-likeness) and absorption, distribution, metabolism, excretion, and toxicity predictions were followed to find a good balance of potency. The selected flavonoids of MEK1 have been refined with 30 (ns) molecular dynamics (MD) simulation. The five selected flavonoids are strongly suggested to be promising potent inhibitors for drug development as anticancer therapeutics of the therapeutic target MEK1. MDPI 2022-02-03 /pmc/articles/PMC8876294/ /pubmed/35215307 http://dx.doi.org/10.3390/ph15020195 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
AlZahrani, Wejdan M.
AlGhamdi, Shareefa A.
Zughaibi, Torki A.
Rehan, Mohd
Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods
title Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods
title_full Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods
title_fullStr Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods
title_full_unstemmed Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods
title_short Exploring the Natural Compounds in Flavonoids for Their Potential Inhibition of Cancer Therapeutic Target MEK1 Using Computational Methods
title_sort exploring the natural compounds in flavonoids for their potential inhibition of cancer therapeutic target mek1 using computational methods
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876294/
https://www.ncbi.nlm.nih.gov/pubmed/35215307
http://dx.doi.org/10.3390/ph15020195
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