New Anti-Seizure (Arylalkyl)azole Derivatives: Synthesis, In Vivo and In Silico Studies

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dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authoridReynisson, Jóhannes/0000-0003-4174-9512
dc.authoridKarakurt, Arzu/0000-0003-2209-0871
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authorwosidSARI, SUAT/A-5249-2017
dc.authorwosidReynisson, Jóhannes/AAL-9886-2021
dc.authorwosidKarakurt, Arzu/ABH-9340-2020
dc.authorwosidSARI, SUAT/JCD-8070-2023
dc.contributor.authorSari, Suat
dc.contributor.authorDalkara, Sevim
dc.contributor.authorKaynak, Filiz Betul
dc.contributor.authorReynisson, Johannes
dc.contributor.authorSarac, Selma
dc.contributor.authorKarakurt, Arzu
dc.date.accessioned2024-08-04T20:43:09Z
dc.date.available2024-08-04T20:43:09Z
dc.date.issued2017
dc.departmentİnönü Üniversitesien_US
dc.description.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 -aminobutyric acid (GABA)-mediated response. LRZ, a positive allosteric modulator of A-type GABA receptors (GABA(A)Rs), was reported to be sensitive to Asn265 of the 2/3 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 GABA(A)R and VGSC homology models. They predicted high affinity to the benzodiazepine binding site of GABA(A)R in line with the experimental results. Also, the binding mode and interactions of LRZ in its putative allosteric binding site of GABA(A)R is elucidated.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [113S060, 115S387, 2214-A]; Hacettepe University Scientific Research Projects Coordination Unit [014 D09 301 001-703, TPT-2015-6794]en_US
dc.description.sponsorshipThis study was funded by The Scientific and Technological Research Council of Turkey (TUBITAK) (grant numbers: 113S060, 115S387, 2214-A) and Hacettepe University Scientific Research Projects Coordination Unit (grant numbers: 014 D09 301 001-703, TPT-2015-6794). We are grateful to the ETSP team of the NINDS for conducting biological experiments. We would like to thank Prof. Dr. Erhan Palaska for providing the mass data.en_US
dc.identifier.doi10.1002/ardp.201700043
dc.identifier.issn0365-6233
dc.identifier.issn1521-4184
dc.identifier.issue6en_US
dc.identifier.pmid28464338en_US
dc.identifier.scopus2-s2.0-85018980032en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1002/ardp.201700043
dc.identifier.urihttps://hdl.handle.net/11616/97807
dc.identifier.volume350en_US
dc.identifier.wosWOS:000402923500004en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWiley-V C H Verlag Gmbhen_US
dc.relation.ispartofArchiv Der Pharmazieen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAllosteric modulationen_US
dc.subjectStructure elucidationen_US
dc.subjectSynthesisen_US
dc.titleNew Anti-Seizure (Arylalkyl)azole Derivatives: Synthesis, In Vivo and In Silico Studiesen_US
dc.typeArticleen_US

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