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Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 Receptors
The blockade of kainate receptors, in particular with non-competitive antagonists, has—due to their anticonvulsant and neuroprotective properties—therapeutic potential in many central nervous system (CNS) diseases. Deciphering the structural properties of kainate receptor ligands is crucial to desig...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032324/ https://www.ncbi.nlm.nih.gov/pubmed/35458681 http://dx.doi.org/10.3390/molecules27082479 |
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author | Bartyzel, Agata Kaczor, Agnieszka A. Mahmoudi, Ghodrat Masoudiasl, Ardavan Wróbel, Tomasz M. Pitucha, Monika Matosiuk, Dariusz |
author_facet | Bartyzel, Agata Kaczor, Agnieszka A. Mahmoudi, Ghodrat Masoudiasl, Ardavan Wróbel, Tomasz M. Pitucha, Monika Matosiuk, Dariusz |
author_sort | Bartyzel, Agata |
collection | PubMed |
description | The blockade of kainate receptors, in particular with non-competitive antagonists, has—due to their anticonvulsant and neuroprotective properties—therapeutic potential in many central nervous system (CNS) diseases. Deciphering the structural properties of kainate receptor ligands is crucial to designing medicinal compounds that better fit the receptor binding pockets. In light of that fact, here, we report experimental and computational structural studies of four indole derivatives that are non-competitive antagonists of GluK1/GluK2 receptors. We used X-ray studies and Hirshfeld surface analysis to determine the structure of the compounds in the solid state and quantum chemical calculations to compute HOMO and LUMO orbitals and the electrostatic potential. Moreover, non-covalent interaction maps were also calculated. It is worth emphasizing that compounds 3 and 4 are achiral molecules crystallising in non-centrosymmetric space groups, which is a relatively rare phenomenon. |
format | Online Article Text |
id | pubmed-9032324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90323242022-04-23 Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 Receptors Bartyzel, Agata Kaczor, Agnieszka A. Mahmoudi, Ghodrat Masoudiasl, Ardavan Wróbel, Tomasz M. Pitucha, Monika Matosiuk, Dariusz Molecules Article The blockade of kainate receptors, in particular with non-competitive antagonists, has—due to their anticonvulsant and neuroprotective properties—therapeutic potential in many central nervous system (CNS) diseases. Deciphering the structural properties of kainate receptor ligands is crucial to designing medicinal compounds that better fit the receptor binding pockets. In light of that fact, here, we report experimental and computational structural studies of four indole derivatives that are non-competitive antagonists of GluK1/GluK2 receptors. We used X-ray studies and Hirshfeld surface analysis to determine the structure of the compounds in the solid state and quantum chemical calculations to compute HOMO and LUMO orbitals and the electrostatic potential. Moreover, non-covalent interaction maps were also calculated. It is worth emphasizing that compounds 3 and 4 are achiral molecules crystallising in non-centrosymmetric space groups, which is a relatively rare phenomenon. MDPI 2022-04-12 /pmc/articles/PMC9032324/ /pubmed/35458681 http://dx.doi.org/10.3390/molecules27082479 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 Bartyzel, Agata Kaczor, Agnieszka A. Mahmoudi, Ghodrat Masoudiasl, Ardavan Wróbel, Tomasz M. Pitucha, Monika Matosiuk, Dariusz Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 Receptors |
title | Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 Receptors |
title_full | Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 Receptors |
title_fullStr | Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 Receptors |
title_full_unstemmed | Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 Receptors |
title_short | Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 Receptors |
title_sort | experimental and computational structural studies of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles as non-competitive antagonists of gluk1/gluk2 receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032324/ https://www.ncbi.nlm.nih.gov/pubmed/35458681 http://dx.doi.org/10.3390/molecules27082479 |
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