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

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dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authoridKarakurt, Arzu/0000-0003-2209-0871
dc.authoridUSLU, HARUN/0000-0001-8827-8557
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authorwosidSARI, SUAT/A-5249-2017
dc.authorwosidKarakurt, Arzu/ABH-9340-2020
dc.authorwosidUSLU, HARUN/P-3681-2019
dc.authorwosidSARI, SUAT/JCD-8070-2023
dc.contributor.authorSari, Suat
dc.contributor.authorKarakurt, Arzu
dc.contributor.authorUslu, Harun
dc.contributor.authorKaynak, F. Betul
dc.contributor.authorCalis, Unsal
dc.contributor.authorDalkara, Sevim
dc.date.accessioned2024-08-04T20:42:38Z
dc.date.available2024-08-04T20:42:38Z
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-yeethanone 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 gamma-aminobutiric acid (GABA)-mediated response. In order to get insights into the effects of our compounds on VGSCs and A type GABA receptors (GABA(A)Rs) we performed docking studies using homology model of Na+ channel inner pore and GABA(A)R 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. (C) 2016 Elsevier Masson SAS. All rights reserved.en_US
dc.identifier.doi10.1016/j.ejmech.2016.08.032
dc.identifier.endpage416en_US
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.pmid27597416en_US
dc.identifier.scopus2-s2.0-84984939482en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage407en_US
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2016.08.032
dc.identifier.urihttps://hdl.handle.net/11616/97491
dc.identifier.volume124en_US
dc.identifier.wosWOS:000388544600033en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevieren_US
dc.relation.ispartofEuropean Journal of Medicinal Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_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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