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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8876294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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