Impact of n-alkylamino substituents on serotonin receptor (5-HTR) affinity and phosphodiesterase 10A (PDE10A) inhibition of isoindole-1,3-dione derivatives
Authors:
- 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
Abstract
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.
- Record ID
- CUT4d6222842bec4f60955091685a19cc04
- Publication categories
- ;
- Author
- Journal series
- Molecules, ISSN , e-ISSN 1420-3049, Biweekly
- Issue year
- 2020
- Vol
- 25
- No
- 17
- Pages
- [1-19]
- Other elements of collation
- rys.; wykr.; Bibliografia (na s.) - 17-19; Bibliografia (liczba pozycji) - 43; Oznaczenie streszczenia - Abstr.; Numeracja w czasopiśmie - Vol. 25, Iss. 17, Spec. Iss.
- Substantive notes
- Tyt. Spec. Iss.: Medicinal Chemistry in Europe II
- Keywords in English
- benzimidazole derivatives, phosphodiesterase 10A, schizophrenia, antipsychotic activity
- DOI
- DOI:10.3390/molecules25173868 Opening in a new tab
- URL
- https://www.mdpi.com/1420-3049/25/17/3868/htm Opening in a new tab
- Language
- eng (en) English
- License
- Score (nominal)
- 140
- Publication indicators
- = 6
- Additional fields
- Indeksowana w: Web of Science, Scopus
- Uniform Resource Identifier
- https://cris.pk.edu.pl/info/article/CUT4d6222842bec4f60955091685a19cc04/
- URN
urn:pkr-prod:CUT4d6222842bec4f60955091685a19cc04
* presented citation count is obtained through Internet information analysis, and it is close to the number calculated by the Publish or PerishOpening in a new tab system.