New arylalkyl azole derivatives showing anticonvulsant effects could have VGSC and or GABAAR affinity according to molecular modeling studies

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dc.authoridTR195285en_US
dc.authoridTR112389en_US
dc.authoridTR38542en_US
dc.authoridTR116133en_US
dc.authoridTR182545en_US
dc.contributor.authorSarı, Suat
dc.contributor.authorKarakurt, Arzu
dc.contributor.authorUslu, Harun
dc.contributor.authorKaynak, Filiz Betül
dc.contributor.authorÇalış, Ünsal
dc.contributor.authorDalkara, Sevim
dc.date.accessioned2017-04-12T07:40:47Z
dc.date.available2017-04-12T07:40:47Z
dc.date.issued2016
dc.departmentİnönü Üniversitesien_US
dc.description.abstract(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.en_US
dc.identifier.citationSarı, 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.en_US
dc.identifier.doi10.1016/j.ejmech.2016.08.032en_US
dc.identifier.endpage416en_US
dc.identifier.issn02235234
dc.identifier.startpage407en_US
dc.identifier.urihttp://linkinghub.elsevier.com/retrieve/pii/S0223523416306754
dc.identifier.urihttps://hdl.handle.net/11616/6644
dc.identifier.volume124en_US
dc.language.isoenen_US
dc.publisherEuropean Journal of Medicinal Chemistryen_US
dc.relation.ispartofEuropean Journal of Medicinal Chemistryen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject(Arylalkyl)azoleen_US
dc.subjectAnticonvulsanten_US
dc.subjectVoltage gated sodium channelen_US
dc.subjectA-type GABA receptoren_US
dc.subjectMolecular dockingen_US
dc.subjectX-ray crystallographyen_US
dc.subjectMicrowave chemistryen_US
dc.titleNew arylalkyl azole derivatives showing anticonvulsant effects could have VGSC and or GABAAR affinity according to molecular modeling studiesen_US
dc.typeArticleen_US

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