Kaczor Agnieszka A, Wróbel Tomasz, Kronbach Christiane, Unverferth Klaus, Stachal Tomasz, Matosiuk Dariusz
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.
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.
Med Chem Res. 2015;24(2):810-817. doi: 10.1007/s00044-014-1171-1. Epub 2014 Jul 24.
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.
在此，我们展示了新型GluK2受体非竞争性拮抗剂的合成、药理活性及分子对接情况。所涉及的化合物为吲哚和咔唑衍生物，是报道的第二类GluK2受体非竞争性拮抗剂（第一类同样由我们团队发表）。吲哚衍生物的活性处于微摩尔范围，与第一类非竞争性GluK2受体拮抗剂的情况相同。我们发现设计的咔唑衍生物没有活性。活性吲哚衍生物与GluK2受体的转导结构域相互作用，即该结构域将受体的跨膜区域与激动剂结合结构域相连。结合口袋位于一个受体亚基内。
