| Autor: |
Anna Czopek, Anna Partyka, Adam Bucki, Maciej Pawłowski, Marcin Kołaczkowski, Agata Siwek, Monika Głuch-Lutwin, Paulina Koczurkiewicz, Elżbieta Pękala, Anna Jaromin, Bożena Tyliszczak, Anna Wesołowska, Agnieszka Zagórska |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Molecules, Vol 25, Iss 17, p 3868 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1420-3049 |
| DOI: |
10.3390/molecules25173868 |
| Popis: |
In this study, a series of compounds derived from 4-methoxy-1H-isoindole-1,3(2H)-dione, potential ligands of phosphodiesterase 10A and serotonin receptors, were investigated as potential antipsychotics. A library of 4-methoxy-1H-isoindole-1,3(2H)-dione derivatives with various amine moieties was synthesized and examined for their phosphodiesterase 10A (PDE10A)-inhibiting properties and their 5-HT1A and 5-HT7 receptor affinities. Based on in vitro studies, the most potent compound, 18 (2-[4-(1H-benzimidazol-2-yl)butyl]-4-methoxy-1H-isoindole-1,3(2H)-dione), was selected and its safety in vitro was evaluated. In order to explain the binding mode of compound 18 in the active site of the PDE10A enzyme and describe the molecular interactions responsible for its inhibition, computer-aided docking studies were performed. The potential antipsychotic properties of compound 18 in a behavioral model of schizophrenia were also investigated. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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