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Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment
Obesity is a pandemic and a serious health problem in developed and undeveloped countries. Activation of estrogen receptor beta (ERβ) has been shown to promote weight loss without modifying caloric intake, making it an attractive target for developing new drugs against obesity. This work aimed to pr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254148/ https://www.ncbi.nlm.nih.gov/pubmed/37298864 http://dx.doi.org/10.3390/molecules28114389 |
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author | Méndez-Álvarez, Domingo Torres-Rojas, Maria F. Lara-Ramirez, Edgar E. Marchat, Laurence A. Rivera, Gildardo |
author_facet | Méndez-Álvarez, Domingo Torres-Rojas, Maria F. Lara-Ramirez, Edgar E. Marchat, Laurence A. Rivera, Gildardo |
author_sort | Méndez-Álvarez, Domingo |
collection | PubMed |
description | Obesity is a pandemic and a serious health problem in developed and undeveloped countries. Activation of estrogen receptor beta (ERβ) has been shown to promote weight loss without modifying caloric intake, making it an attractive target for developing new drugs against obesity. This work aimed to predict new small molecules as potential ERβ activators. A ligand-based virtual screening of the ZINC15, PubChem, and Molport databases by substructure and similarity was carried out using the three-dimensional organization of known ligands as a reference. A molecular docking screening of FDA-approved drugs was also conducted as a repositioning strategy. Finally, selected compounds were evaluated by molecular dynamic simulations. Compounds 1 (−24.27 ± 0.34 kcal/mol), 2 (−23.33 ± 0.3 kcal/mol), and 6 (−29.55 ± 0.51 kcal/mol) showed the best stability on the active site in complex with ERβ with an RMSD < 3.3 Å. RMSF analysis showed that these compounds do not affect the fluctuation of the Cα of ERβ nor the compactness according to the radius of gyration. Finally, an in silico evaluation of ADMET showed they are safe molecules. These results suggest that new ERβ ligands could be promising molecules for obesity control. |
format | Online Article Text |
id | pubmed-10254148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102541482023-06-10 Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment Méndez-Álvarez, Domingo Torres-Rojas, Maria F. Lara-Ramirez, Edgar E. Marchat, Laurence A. Rivera, Gildardo Molecules Article Obesity is a pandemic and a serious health problem in developed and undeveloped countries. Activation of estrogen receptor beta (ERβ) has been shown to promote weight loss without modifying caloric intake, making it an attractive target for developing new drugs against obesity. This work aimed to predict new small molecules as potential ERβ activators. A ligand-based virtual screening of the ZINC15, PubChem, and Molport databases by substructure and similarity was carried out using the three-dimensional organization of known ligands as a reference. A molecular docking screening of FDA-approved drugs was also conducted as a repositioning strategy. Finally, selected compounds were evaluated by molecular dynamic simulations. Compounds 1 (−24.27 ± 0.34 kcal/mol), 2 (−23.33 ± 0.3 kcal/mol), and 6 (−29.55 ± 0.51 kcal/mol) showed the best stability on the active site in complex with ERβ with an RMSD < 3.3 Å. RMSF analysis showed that these compounds do not affect the fluctuation of the Cα of ERβ nor the compactness according to the radius of gyration. Finally, an in silico evaluation of ADMET showed they are safe molecules. These results suggest that new ERβ ligands could be promising molecules for obesity control. MDPI 2023-05-27 /pmc/articles/PMC10254148/ /pubmed/37298864 http://dx.doi.org/10.3390/molecules28114389 Text en © 2023 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 Méndez-Álvarez, Domingo Torres-Rojas, Maria F. Lara-Ramirez, Edgar E. Marchat, Laurence A. Rivera, Gildardo Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment |
title | Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment |
title_full | Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment |
title_fullStr | Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment |
title_full_unstemmed | Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment |
title_short | Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment |
title_sort | ligand-based virtual screening, molecular docking, and molecular dynamic simulations of new β-estrogen receptor activators with potential for pharmacological obesity treatment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254148/ https://www.ncbi.nlm.nih.gov/pubmed/37298864 http://dx.doi.org/10.3390/molecules28114389 |
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