Tools
ToolsGonzález-Vera, Juan A., Medina, Rocío A., Martín-Fontecha, Mar, Gonzalez, Angel, de la Fuente, Tania, Vázquez-Villa, Henar, García-Cárceles, Javier, Botta, Joaquín, McCormick, Peter J., Benhamú, Bellinda, Pardo, Leonardo and López-Rodríguez, María L. (2017) A new serotonin 5-HT6 receptor antagonist with procognitive activity – Importance of a halogen bond interaction to stabilize the binding. Scientific Reports, 7. ISSN 2045-2322
Preview |
PDF (Published manuscript)
- Published Version
Available under License Creative Commons Attribution. Download (1MB) | Preview |
Abstract
Serotonin 5-HT6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer’s disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science > School of Pharmacy |
| Related URLs: | |
| Depositing User: | Pure Connector |
| Date Deposited: | 02 Feb 2017 03:49 |
| Last Modified: | 22 Oct 2022 02:11 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/62278 |
| DOI: | 10.1038/srep41293 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |