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Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors

The physiological responses to estrogen hormones are mediated within specific tissues by at least two distinct receptors, ERα and ERβ. Several natural and synthetic molecules show activity by interacting with these proteins. In particular, a number of vegetal compounds known as phytoestrogens shows...

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Autores principales: Grande, Fedora, Rizzuti, Bruno, Occhiuzzi, Maria A., Ioele, Giuseppina, Casacchia, Teresa, Gelmini, Fabrizio, Guzzi, Rita, Garofalo, Antonio, Statti, Giancarlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017050/
https://www.ncbi.nlm.nih.gov/pubmed/29649162
http://dx.doi.org/10.3390/molecules23040894
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author Grande, Fedora
Rizzuti, Bruno
Occhiuzzi, Maria A.
Ioele, Giuseppina
Casacchia, Teresa
Gelmini, Fabrizio
Guzzi, Rita
Garofalo, Antonio
Statti, Giancarlo
author_facet Grande, Fedora
Rizzuti, Bruno
Occhiuzzi, Maria A.
Ioele, Giuseppina
Casacchia, Teresa
Gelmini, Fabrizio
Guzzi, Rita
Garofalo, Antonio
Statti, Giancarlo
author_sort Grande, Fedora
collection PubMed
description The physiological responses to estrogen hormones are mediated within specific tissues by at least two distinct receptors, ERα and ERβ. Several natural and synthetic molecules show activity by interacting with these proteins. In particular, a number of vegetal compounds known as phytoestrogens shows estrogenic or anti-estrogenic activity. The majority of these compounds belongs to the isoflavones family and the most representative one, genistein, shows anti-proliferative effects on various hormone-sensitive cancer cells, including breast, ovarian and prostate cancer. In this work we describe the identification of structurally related homoisoflavones isolated from Leopoldia comosa (L.) Parl. (L. comosa), a perennial bulbous plant, potentially useful as hormonal substitutes or complements in cancer treatments. Two of these compounds have been selected as potential ligands of estrogen receptors (ERs) and the interaction with both isoforms of estrogen receptors have been investigated through molecular docking on their crystallographic structures. The results provide evidence of the binding of these compounds to the target receptors and their interactions with key residues of the active sites of the two proteins, and thus they could represent suitable leads for the development of novel tools for the dissection of ER signaling and the development of new pharmacological treatments in hormone-sensitive cancers.
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spelling pubmed-60170502018-11-13 Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors Grande, Fedora Rizzuti, Bruno Occhiuzzi, Maria A. Ioele, Giuseppina Casacchia, Teresa Gelmini, Fabrizio Guzzi, Rita Garofalo, Antonio Statti, Giancarlo Molecules Article The physiological responses to estrogen hormones are mediated within specific tissues by at least two distinct receptors, ERα and ERβ. Several natural and synthetic molecules show activity by interacting with these proteins. In particular, a number of vegetal compounds known as phytoestrogens shows estrogenic or anti-estrogenic activity. The majority of these compounds belongs to the isoflavones family and the most representative one, genistein, shows anti-proliferative effects on various hormone-sensitive cancer cells, including breast, ovarian and prostate cancer. In this work we describe the identification of structurally related homoisoflavones isolated from Leopoldia comosa (L.) Parl. (L. comosa), a perennial bulbous plant, potentially useful as hormonal substitutes or complements in cancer treatments. Two of these compounds have been selected as potential ligands of estrogen receptors (ERs) and the interaction with both isoforms of estrogen receptors have been investigated through molecular docking on their crystallographic structures. The results provide evidence of the binding of these compounds to the target receptors and their interactions with key residues of the active sites of the two proteins, and thus they could represent suitable leads for the development of novel tools for the dissection of ER signaling and the development of new pharmacological treatments in hormone-sensitive cancers. MDPI 2018-04-12 /pmc/articles/PMC6017050/ /pubmed/29649162 http://dx.doi.org/10.3390/molecules23040894 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Grande, Fedora
Rizzuti, Bruno
Occhiuzzi, Maria A.
Ioele, Giuseppina
Casacchia, Teresa
Gelmini, Fabrizio
Guzzi, Rita
Garofalo, Antonio
Statti, Giancarlo
Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors
title Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors
title_full Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors
title_fullStr Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors
title_full_unstemmed Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors
title_short Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors
title_sort identification by molecular docking of homoisoflavones from leopoldia comosa as ligands of estrogen receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017050/
https://www.ncbi.nlm.nih.gov/pubmed/29649162
http://dx.doi.org/10.3390/molecules23040894
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