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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...

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Autores principales: de Almeida, Vitor Martins, Santos-Filho, Osvaldo Andrade
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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