Microwave-assisted synthesis of trazodone and its derivatives as new 5-HT1A ligands: binding and docking studies
Authors:
- Jolanta Jaśkowska,
- Przemysław Zaręba,
- Paweł Śliwa,
- Edyta Pindelska,
- Grzegorz Satała,
- Zbigniew Majka
Abstract
Trazodone, a well-known antidepressant drug widely used throughout the world, works as a 5-hydroxytryptamine (5-HT2) and α1-adrenergic receptor antagonist and a serotonin reuptake inhibitor. Our research aimed to develop a new method for the synthesis of trazodone and its derivatives. In the known methods of the synthesis of trazodone and its derivatives, organic and toxic solvents are used, and the synthesis time varies from several to several dozen hours. Our research shows that trazodone and its derivatives can be successfully obtained in the presence of potassium carbonate as a reaction medium in the microwave field in a few minutes. As a result of the research work, 17 derivatives of trazodone were obtained, including compounds that exhibit the characteristics of 5-HT1A receptor ligands. Molecular modeling studies were performed to understand the differences in the activity toward 5-HT1A and 5-HT2A receptors between ligand 10a (2-(6-(4-(3-chlorophenyl)piperazin-1-yl)hexyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one) (5-HT1A Ki = 16 nM) and trazodone. The docking results indicate the lack of the binding of ligand 10a to 5-HT2AR, which is consistent with the in vitro studies. On the other hand, the docking results for the 5-HT1A receptor indicate two possible binding modes. Crystallographic studies support the hypothesis of an extended conformation.
- Record ID
- CUT5da28f52b2a642279178ef9c8aa89f69
- Publication categories
- ;
- Author
- Other language title versions
- Microwave-assisted synthesis of trazodone and its derivatives as new 5-HT1A ligands: binding and docking studies
- Journal series
- Molecules, ISSN , e-ISSN 1420-3049, Biweekly
- Issue year
- 2019
- Vol
- 24
- No
- 8
- Pages
- [1-19]
- Article number
- 1609
- Other elements of collation
- rys.; schem.; tab.; Bibliografia (na s.) - 18-19; Bibliografia (liczba pozycji) - 27; Oznaczenie streszczenia - Abstr.; Numeracja w czasopiśmie - Vol. 24, Iss. 8, Spec. Iss.
- Substantive notes
- Special Issue: Sustainable Synthesis
- Keywords in English
- trazodone derivatives, trazodone synthesis, microwave (MW)-assisted synthesis, serotonin receptor ligands, 5-HT1A ligands, long-chain arylpiperazines
- DOI
- DOI:10.3390/molecules24081609 Opening in a new tab
- URL
- https://www.mdpi.com/1420-3049/24/8/1609 Opening in a new tab
- Language
- eng (en) English
- License
- Score (nominal)
- 140
- Additional fields
- Indeksowana w: Web of Science, Scopus
- Uniform Resource Identifier
- https://cris.pk.edu.pl/info/article/CUT5da28f52b2a642279178ef9c8aa89f69/
- URN
urn:pkr-prod:CUT5da28f52b2a642279178ef9c8aa89f69
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