title: Synthesis and molecular docking of novel non-competitive antagonists of GluK2 receptor.
abstract: Here we present the synthesis, pharmacological activity, and molecular docking of novel non-competitive antagonists of GluK2 receptor. The compounds concerned are derivatives of indole and carbazole and are the second reported series of non-competitive antagonists of the GluK2 receptor (the first one was also published by our group). The activity of the indole derivatives is in the micromolar range, as in the case of the first series of non-competitive GluK2 receptor antagonists. We have found that designed carbazole derivatives are devoid of activity. Active indole derivatives interact with the transduction domain of the GluK2 receptor, i.e., the domain which links the transmembrane region of the receptor with the agonist-binding domain. The binding pocket is situated within one receptor subunit.
authors.affiliation: Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, ul. Chodźki 4A, 20093 Lublin, Poland ; School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, 1627, 70211 Kuopio, Finland.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Kaczor
authors.affiliation: Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, ul. Chodźki 4A, 20093 Lublin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wróbel
authors.affiliation: Biotie Therapie GmbH, Meissner Str. 191, 01445 Radebul, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kronbach
authors.affiliation: Biotie Therapie GmbH, Meissner Str. 191, 01445 Radebul, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Unverferth
authors.affiliation: Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, ul. Chodźki 4A, 20093 Lublin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Stachal
authors.affiliation: Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, ul. Chodźki 4A, 20093 Lublin, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Matosiuk
keywords: Carbazole derivatives; Indole derivatives; Kainate receptors; Non-competitive GluK2 receptor antagonists