Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands

The synthesis of seventeen new 1,3-diaryl-5-oxo-proline derivatives as endothelin receptor (ETR) ligands is described. The structural configuration of the new molecules was determined by analyzing selected signals in proton NMR spectra. In vitro binding assays of the human ET(A) and ET(B) receptors...

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Autores principales: Intagliata, Sebastiano, Helal, Mohamed A., Materia, Luisa, Pittalà, Valeria, Salerno, Loredana, Marrazzo, Agostino, Cagnotto, Alfredo, Salmona, Mario, Modica, Maria N., Romeo, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221592/
https://www.ncbi.nlm.nih.gov/pubmed/32316541
http://dx.doi.org/10.3390/molecules25081851
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author Intagliata, Sebastiano
Helal, Mohamed A.
Materia, Luisa
Pittalà, Valeria
Salerno, Loredana
Marrazzo, Agostino
Cagnotto, Alfredo
Salmona, Mario
Modica, Maria N.
Romeo, Giuseppe
author_facet Intagliata, Sebastiano
Helal, Mohamed A.
Materia, Luisa
Pittalà, Valeria
Salerno, Loredana
Marrazzo, Agostino
Cagnotto, Alfredo
Salmona, Mario
Modica, Maria N.
Romeo, Giuseppe
author_sort Intagliata, Sebastiano
collection PubMed
description The synthesis of seventeen new 1,3-diaryl-5-oxo-proline derivatives as endothelin receptor (ETR) ligands is described. The structural configuration of the new molecules was determined by analyzing selected signals in proton NMR spectra. In vitro binding assays of the human ET(A) and ET(B) receptors allowed us to identify compound 31h as a selective ET(A)R ligand. The molecular docking of the selected compounds and the ET(A) antagonist atrasentan in the ET(A)R homology model provided insight into the structural elements required for the affinity and the selectivity of the ET(A)R subtype.
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spelling pubmed-72215922020-05-22 Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands Intagliata, Sebastiano Helal, Mohamed A. Materia, Luisa Pittalà, Valeria Salerno, Loredana Marrazzo, Agostino Cagnotto, Alfredo Salmona, Mario Modica, Maria N. Romeo, Giuseppe Molecules Article The synthesis of seventeen new 1,3-diaryl-5-oxo-proline derivatives as endothelin receptor (ETR) ligands is described. The structural configuration of the new molecules was determined by analyzing selected signals in proton NMR spectra. In vitro binding assays of the human ET(A) and ET(B) receptors allowed us to identify compound 31h as a selective ET(A)R ligand. The molecular docking of the selected compounds and the ET(A) antagonist atrasentan in the ET(A)R homology model provided insight into the structural elements required for the affinity and the selectivity of the ET(A)R subtype. MDPI 2020-04-17 /pmc/articles/PMC7221592/ /pubmed/32316541 http://dx.doi.org/10.3390/molecules25081851 Text en © 2020 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
Intagliata, Sebastiano
Helal, Mohamed A.
Materia, Luisa
Pittalà, Valeria
Salerno, Loredana
Marrazzo, Agostino
Cagnotto, Alfredo
Salmona, Mario
Modica, Maria N.
Romeo, Giuseppe
Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands
title Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands
title_full Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands
title_fullStr Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands
title_full_unstemmed Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands
title_short Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands
title_sort synthesis and molecular modelling studies of new 1,3-diaryl-5-oxo-proline derivatives as endothelin receptor ligands
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221592/
https://www.ncbi.nlm.nih.gov/pubmed/32316541
http://dx.doi.org/10.3390/molecules25081851
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