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.

Indoles / pharmacology Ligands Protein Binding Receptors, Kainic Acid / chemistry
X-ray studies indole derivatives kainate receptor ligands quantum chemical calculations

Journal

Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009

Informations de publication

Date de publication:
12 Apr 2022
Historique:
received: 15 03 2022
revised: 01 04 2022
accepted: 07 04 2022
entrez: 23 4 2022
pubmed: 24 4 2022
medline: 27 4 2022
Statut: epublish

Résumé

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

Identifiants

DOI: 10.3390/molecules27082479 PMID: 35458681 PMC: PMC9032324
pubmed: 35458681
pii: molecules27082479
doi: 10.3390/molecules27082479
pmc: PMC9032324
pii:
doi:

Substances chimiques

Indoles 0
Ligands 0
Receptors, Kainic Acid 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Références

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Auteurs

Agata Bartyzel (A)

Department 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, Poland.
ORCID: 0000-0003-3765-6997

Agnieszka A Kaczor (AA)

Pharmaceutical Substances with Computer Modeling Laboratory, Department of Synthesis and Chemical Technology, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki St., PL-20093 Lublin, Poland.
School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland.
ORCID: 0000-0001-8679-9623

Ghodrat Mahmoudi (G)

Department of Chemistry, Faculty of Science, University of Maragheh, Maragheh P.O. Box 55181-83111, Iran.

Ardavan Masoudiasl (A)

Department of Chemistry, Faculty of Science, University of Maragheh, Maragheh P.O. Box 55181-83111, Iran.

Tomasz M Wróbel (TM)

Pharmaceutical Substances with Computer Modeling Laboratory, Department of Synthesis and Chemical Technology, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki St., PL-20093 Lublin, Poland.
ORCID: 0000-0002-0313-2522

Monika Pitucha (M)

Independent Radiopharmacy Unit, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki St., PL-20093 Lublin, Poland.
ORCID: 0000-0001-8792-1029

Dariusz Matosiuk (D)

Pharmaceutical Substances with Computer Modeling Laboratory, Department of Synthesis and Chemical Technology, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki St., PL-20093 Lublin, Poland.
ORCID: 0000-0002-2373-9479

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Classifications MeSH

Recherchemedicale.com › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Indoles › Experimental and Computational Structural...
Recherchemedicale.com › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › Experimental and Computational Structural...
Recherchemedicale.com › Métabolisme › Liaison aux protéines › Experimental and Computational Structural...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs aux acides aminés › Récepteurs au glutamate › Récepteurs ionotropes du glutamate › Récepteurs kaïnate › Experimental and Computational Structural...