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...
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MDPI AG
2022-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/8/2479 |
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| author | Agata Bartyzel Agnieszka A. Kaczor Ghodrat Mahmoudi Ardavan Masoudiasl Tomasz M. Wróbel Monika Pitucha Dariusz Matosiuk |
| author_facet | Agata Bartyzel Agnieszka A. Kaczor Ghodrat Mahmoudi Ardavan Masoudiasl Tomasz M. Wróbel Monika Pitucha Dariusz Matosiuk |
| author_sort | Agata Bartyzel |
| collection | DOAJ |
| 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 <b>3</b> and <b>4</b> are achiral molecules crystallising in non-centrosymmetric space groups, which is a relatively rare phenomenon. |
| first_indexed | 2024-03-09T10:31:24Z |
| format | Article |
| id | doaj.art-af9c3d63e8d34b4d9ebca28368def855 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T10:31:24Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-af9c3d63e8d34b4d9ebca28368def8552023-12-01T21:16:05ZengMDPI AGMolecules1420-30492022-04-01278247910.3390/molecules27082479Experimental and Computational Structural Studies of 2,3,5-Trisubstituted and 1,2,3,5-Tetrasubstituted Indoles as Non-Competitive Antagonists of GluK1/GluK2 ReceptorsAgata Bartyzel0Agnieszka A. Kaczor1Ghodrat Mahmoudi2Ardavan Masoudiasl3Tomasz M. Wróbel4Monika Pitucha5Dariusz Matosiuk6Department of General and Coordination Chemistry and Crystallography, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University in Lublin, M. Curie-Skłodowskiej Sq. 2, PL-20031 Lublin, PolandPharmaceutical Substances with Computer Modeling Laboratory, Department of Synthesis and Chemical Technology, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki St., PL-20093 Lublin, PolandDepartment of Chemistry, Faculty of Science, University of Maragheh, Maragheh P.O. Box 55181-83111, IranDepartment of Chemistry, Faculty of Science, University of Maragheh, Maragheh P.O. Box 55181-83111, IranPharmaceutical Substances with Computer Modeling Laboratory, Department of Synthesis and Chemical Technology, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki St., PL-20093 Lublin, PolandIndependent Radiopharmacy Unit, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki St., PL-20093 Lublin, PolandPharmaceutical Substances with Computer Modeling Laboratory, Department of Synthesis and Chemical Technology, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki St., PL-20093 Lublin, PolandThe 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 <b>3</b> and <b>4</b> are achiral molecules crystallising in non-centrosymmetric space groups, which is a relatively rare phenomenon.https://www.mdpi.com/1420-3049/27/8/2479indole derivativeskainate receptor ligandsquantum chemical calculationsX-ray studies |
| spellingShingle | Agata Bartyzel Agnieszka A. Kaczor Ghodrat Mahmoudi Ardavan Masoudiasl Tomasz M. Wróbel Monika Pitucha Dariusz Matosiuk 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 Molecules indole derivatives kainate receptor ligands quantum chemical calculations X-ray studies |
| 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 | indole derivatives kainate receptor ligands quantum chemical calculations X-ray studies |
| url | https://www.mdpi.com/1420-3049/27/8/2479 |
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