New arylalkyl azole derivatives showing anticonvulsant effects could have VGSC and or GABAAR affinity according to molecular modeling studies
Yükleniyor...
Dosyalar
Tarih
2016
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
European Journal of Medicinal Chemistry
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
(Arylalkyl)azoles (AAAs) emerged as a novel class of antiepileptic agents with the invention of nafimidone
and denzimol. Several AAA derivatives with potent anticonvulsant activities have been reported so
far, however neurotoxicity was usually an issue. We prepared a set of ester derivatives of 1-(2-naphthyl)-
2-(1H-1,2,4-triazol-1-yl)ethanone oxime and evaluated their anticonvulsant and neurotoxic effects in
mice. Most of our compounds were protective against maximal electroshock (MES)- and/or subcutaneous
metrazol (s.c. MET)-induced seizures whereas none of them showed neurotoxicity. Nafimidone
and denzimol have an activity profile similar to that of phenytoin or carbamazepine, both of which are
known to inhibit voltage-gated sodium channels (VGSCs) as well as to enhance g-aminobutiric acid
(GABA)-mediated response. In order to get insights into the effects of our compounds on VGSCs and Atype
GABA receptors (GABAARs) we performed docking studies using homology model of Naþ channel
inner pore and GABAAR as docking scaffolds. We found that our compounds bind VGSCs in similar ways
as phenytoin, carbamazepine, and lamotrigine. They showed strong affinity to benzodiazepine (BZD)
binding site and their binding interactions were mainly complied with the experimental data and the
reported BZD binding model.
Açıklama
Anahtar Kelimeler
(Arylalkyl)azole, Anticonvulsant, Voltage gated sodium channel, A-type GABA receptor, Molecular docking, X-ray crystallography, Microwave chemistry
Kaynak
European Journal of Medicinal Chemistry
WoS Q Değeri
Scopus Q Değeri
Cilt
124
Sayı
Künye
Sarı, S. Karakurt, A. Uslu, H. Kaynak, F. B. Çalış, Ü. Dalkara, S. (2016). New arylalkyl azole derivatives showing anticonvulsant effects could have VGSC and or GABAAR affinity according to molecular modeling studies. European Journal of Medicinal Chemistry, 124, 407–416.
