Synthesis and pharmacological characterisation of arctigenin analogues as antagonists of AMPA and kainate receptors.
Org Biomol Chem
; 19(42): 9154-9162, 2021 11 03.
Article
em En
| MEDLINE
| ID: mdl-34642722
ABSTRACT
(-)-Arctigenin and a series of new analogues have been synthesised and then tested for their potential as AMPA and kainate receptor antagonists of human homomeric GluA1 and GluK2 receptors expressed in HEK293 cells using a Ca2+ influx assay. In general, these compounds showed antagonist activity at both receptors with greater activity evident at AMPARs. Schild analysis indicates that a spirocyclic analogue 6c acts as a non-competitive antagonist. Molecular docking studies in which 6c was docked into the X-ray crystal structure of the GluA2 tetramer suggest that (-)-arctigenin and its analogues bind in the transmembrane domain in a similar manner to the known AMPA receptor non-competitive antagonists GYKI53655 and the antiepileptic drug perampanel. The arctigenin derivatives described herein may serve as novel leads for the development of drugs for the treatment of epilepsy.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Ácido Caínico
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article