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.
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.
Molecules. 2022 Apr 12;27(8):2479. doi: 10.3390/molecules27082479.
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 and are achiral molecules crystallising in non-centrosymmetric space groups, which is a relatively rare phenomenon.
亲环素抑制剂，特别是非竞争性拮抗剂，由于其具有抗惊厥和神经保护作用，因此在许多中枢神经系统（CNS）疾病中具有治疗潜力。阐明亲环素受体配体的结构特性对于设计更适合受体结合口袋的药物化合物至关重要。有鉴于此，在这里，我们报告了对四种吲哚衍生物的实验和计算结构研究，这些化合物是非 GluK1/GluK2 受体的竞争性拮抗剂。我们使用 X 射线研究和 Hirshfeld 表面分析来确定化合物在固态中的结构，并进行量子化学计算以计算 HOMO 和 LUMO 轨道和静电势。此外，还计算了非共价相互作用图。值得强调的是，化合物 和 是手性分子，在非中心对称空间群中结晶，这是一种相对罕见的现象。
