New Anti-Seizure (Arylalkyl)azole Derivatives: Synthesis, In Vivo and In Silico Studies.
Arch Pharm (Weinheim)
; 350(6)2017 Jun.
Article
en En
| MEDLINE
| ID: mdl-28464338
ABSTRACT
(Arylalkyl)azoles are a class of antiepileptic compounds including nafimidone, denzimol, and loreclezole (LRZ). Nafimidone and denzimol are thought to inhibit voltage-gated sodium channels (VGSCs) and enhance γ-aminobutyric acid (GABA)-mediated response. LRZ, a positive allosteric modulator of A-type GABA receptors (GABAA Rs), was reported to be sensitive to Asn265 of the ß2/ß3 subunit. Here, we report new N-[1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethylidene]hydroxylamine esters showing anticonvulsant activity in animal models, including the 6-Hz psychomotor seizure test, a model for therapy-resistant partial seizure. We performed molecular docking studies for our active compounds using GABAA R and VGSC homology models. They predicted high affinity to the benzodiazepine binding site of GABAA R in line with the experimental results. Also, the binding mode and interactions of LRZ in its putative allosteric binding site of GABAA R is elucidated.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Convulsiones
/
Azoles
/
Simulación del Acoplamiento Molecular
/
Anticonvulsivantes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Año:
2017
Tipo del documento:
Article
País de afiliación:
Turquía