3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity

We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramin...

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Autores principales: Angelina, Emilio Luis, Andujar, Sebastian Antonio, Moreno, Laura, Garibotto, Francisco, Párraga, Javier, Peruchena, Nelida, Cabedo, Nuria, Villecco, Margarita, Cortes, Diego, Enriz, Ricardo Daniel
Formato: Artículo
Lenguaje:Inglés
Publicado: Wiley Online Library 2025
Materias:
3-chlorotyramine
MD simulations
QTAIM análisis
D2 dopamine receptor
Acceso en línea:http://repositorio.unne.edu.ar/handle/123456789/56488
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RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE) de Universidad Nacional del Nordeste
id I48-R184-123456789-56488
record_format dspace
spelling I48-R184-123456789-564882025-03-18T15:23:30Z 3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity Angelina, Emilio Luis Andujar, Sebastian Antonio Moreno, Laura Garibotto, Francisco Párraga, Javier Peruchena, Nelida Cabedo, Nuria Villecco, Margarita Cortes, Diego Enriz, Ricardo Daniel 3-chlorotyramine MD simulations QTAIM análisis D2 dopamine receptor We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2-DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2-DR to that reported for DA. 2025-03-18T14:30:59Z 2025-03-18T14:30:59Z 2015 Artículo Angelina, Emilio Luis, et al., 2015. 3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity. Molecular Informatics. Weinheim: Wiley Online Library, vol. 34, no. 1, p. 28-43. E-ISSN: 1868-1751. 1868-1743 http://repositorio.unne.edu.ar/handle/123456789/56488 eng https://pubmed.ncbi.nlm.nih.gov/27490860/ openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf p. 28-43 application/pdf Wiley Online Library Molecular Informatics, 2015, vol. 34, no. 1, p. 28-43.
institution Universidad Nacional del Nordeste
institution_str I-48
repository_str R-184
collection RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE)
language Inglés
topic 3-chlorotyramine
MD simulations
QTAIM análisis
D2 dopamine receptor
spellingShingle 3-chlorotyramine
MD simulations
QTAIM análisis
D2 dopamine receptor
Angelina, Emilio Luis
Andujar, Sebastian Antonio
Moreno, Laura
Garibotto, Francisco
Párraga, Javier
Peruchena, Nelida
Cabedo, Nuria
Villecco, Margarita
Cortes, Diego
Enriz, Ricardo Daniel
3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity
topic_facet 3-chlorotyramine
MD simulations
QTAIM análisis
D2 dopamine receptor
description We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2-DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2-DR to that reported for DA.
format Artículo
author Angelina, Emilio Luis
Andujar, Sebastian Antonio
Moreno, Laura
Garibotto, Francisco
Párraga, Javier
Peruchena, Nelida
Cabedo, Nuria
Villecco, Margarita
Cortes, Diego
Enriz, Ricardo Daniel
author_facet Angelina, Emilio Luis
Andujar, Sebastian Antonio
Moreno, Laura
Garibotto, Francisco
Párraga, Javier
Peruchena, Nelida
Cabedo, Nuria
Villecco, Margarita
Cortes, Diego
Enriz, Ricardo Daniel
author_sort Angelina, Emilio Luis
title 3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity
title_short 3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity
title_full 3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity
title_fullStr 3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity
title_full_unstemmed 3-Chlorotyramine acting as ligand of the D2 dopamine receptor. Molecular modeling, synthesis and D2 receptor affinity
title_sort 3-chlorotyramine acting as ligand of the d2 dopamine receptor. molecular modeling, synthesis and d2 receptor affinity
publisher Wiley Online Library
publishDate 2025
url http://repositorio.unne.edu.ar/handle/123456789/56488
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