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Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation
Ligand and structure-based computational screenings were carried out to identify flavonoids with potential anticancer activity. Kushenol E, a flavonoid with proven anticancer activity and, at the same time, an allosteric site binder of the enzyme indoleamine 2,3-dioxygenase-1 (IDO1), was used as the...
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/PMC9502501/ https://www.ncbi.nlm.nih.gov/pubmed/36145319 http://dx.doi.org/10.3390/ph15091099 |
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author | de Almeida, Vitor Martins Santos-Filho, Osvaldo Andrade |
author_facet | de Almeida, Vitor Martins Santos-Filho, Osvaldo Andrade |
author_sort | de Almeida, Vitor Martins |
collection | PubMed |
description | Ligand and structure-based computational screenings were carried out to identify flavonoids with potential anticancer activity. Kushenol E, a flavonoid with proven anticancer activity and, at the same time, an allosteric site binder of the enzyme indoleamine 2,3-dioxygenase-1 (IDO1), was used as the reference compound. Molecular docking and molecular dynamics simulations were performed for the screened flavonoids with known anticancer activity. The following two of these flavonoids were identified as potential inhibitors of IDO1: dichamanetin and isochamanetin. Molecular dynamics simulations were used to assess the conformational profile of IDO1-flavonoids complexes, as well as for calculating the bind-free energies. |
format | Online Article Text |
id | pubmed-9502501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95025012022-09-24 Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation de Almeida, Vitor Martins Santos-Filho, Osvaldo Andrade Pharmaceuticals (Basel) Article Ligand and structure-based computational screenings were carried out to identify flavonoids with potential anticancer activity. Kushenol E, a flavonoid with proven anticancer activity and, at the same time, an allosteric site binder of the enzyme indoleamine 2,3-dioxygenase-1 (IDO1), was used as the reference compound. Molecular docking and molecular dynamics simulations were performed for the screened flavonoids with known anticancer activity. The following two of these flavonoids were identified as potential inhibitors of IDO1: dichamanetin and isochamanetin. Molecular dynamics simulations were used to assess the conformational profile of IDO1-flavonoids complexes, as well as for calculating the bind-free energies. MDPI 2022-09-02 /pmc/articles/PMC9502501/ /pubmed/36145319 http://dx.doi.org/10.3390/ph15091099 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 de Almeida, Vitor Martins Santos-Filho, Osvaldo Andrade Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation |
title | Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation |
title_full | Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation |
title_fullStr | Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation |
title_full_unstemmed | Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation |
title_short | Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation |
title_sort | identification of potential allosteric site binders of indoleamine 2,3-dioxygenase 1 from plants: a virtual and molecular dynamics investigation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502501/ https://www.ncbi.nlm.nih.gov/pubmed/36145319 http://dx.doi.org/10.3390/ph15091099 |
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