Design, synthesis and biological evaluation of novel 1,3,5-triazines: effect of aromatic ring decoration on affinity to 5-HT7 receptor
Authors:
- Damian Kułaga,
- Anna Karolina Drabczyk,
- Grzegorz Satała,
- Gniewomir Latacz,
- Anna Boguszewska-Czubara,
- Damian Plażuk,
- Jolanta Jaśkowska
Abstract
Considering the key functions of the 5-HT7 receptor, especially in psychiatry, and the fact that effective and selective 5-HT7 receptor ligands are yet to be available, in this work, we designed and synthesized novel 1,3,5-triazine derivatives particularly based on the evaluation of the effect of substituents at aromatic rings on biological activity. The tested compounds showed high affinity to the 5-HT7 receptor, particularly ligands N2 -(2-(5-fluoro-1H-indol-3-yl)ethyl)-N4 -phenethyl-1,3,5-triazine2,4,6-triamine 2 (Ki = 8 nM) and N2 -(2-(1H-indol-3-yl)ethyl)-N4 -(2-((4-fluorophenyl)amino)ethyl)1,3,5-triazine-2,4,6-triamine 12 (Ki = 18 nM) which showed moderate metabolic stability, and affinity to the CYP3A4 isoenzyme. As for the hepatotoxicity evaluation, the tested compounds showed moderate cytotoxicity only at concentrations above 50 µM. Compound 12 exhibited less cardiotoxic effect than 2 on Danio rerio in vivo model.
- Record ID
- CUTd4f62e35bd6f4ce897a7eef089c0575f
- Publication categories
- ;
- Author
- Journal series
- International Journal of Molecular Sciences, ISSN 1661-6596, e-ISSN 1422-0067, Biweekly
- Issue year
- 2022
- Vol
- 23
- No
- 21
- Pages
- [1-24]
- Article number
- 13308
- Other elements of collation
- fot.; rys.; schem.; tab.; wykr.; Bibliografia (na s.) - 23-24; Bibliografia (liczba pozycji) - 35; Oznaczenie streszczenia - Abstr.; Numeracja w czasopiśmie - Vol. 23, Iss. 21
- Substantive notes
- This article belongs to the Collection: G Protein-Coupled Receptors and Their Kinases in Cell Biology and Disease
- Keywords in English
- serotonin, microwave synthesis, CNS
- ASJC Classification
- ; ; ; ; ; ; ;
- DOI
- DOI:10.3390/ijms232113308 Opening in a new tab
- URL
- https://www.mdpi.com/1422-0067/23/21/13308 Opening in a new tab
- Related project
- Innowacyjne związki first-in-class, jako ligandy receptora 5-HT7 w leczeniu potrójnie negatywnego raka piersi TNBC. . Project leader at PK: , ,
Projects financed by NCRD [Projekty finansowane przez NCBiR (NCBR (] - Language
- eng (en) English
- License
- Score (nominal)
- 140
- Score source
- journalList
- Score
- Publication indicators
- Additional fields
- Indeksowana w: Web of Science, Scopus
- Uniform Resource Identifier
- https://cris.pk.edu.pl/info/article/CUTd4f62e35bd6f4ce897a7eef089c0575f/
- URN
urn:pkr-prod:CUTd4f62e35bd6f4ce897a7eef089c0575f
* 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.