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dc.contributor.authorSever, Belgin
dc.contributor.authorAltıntop, Mehlika Dilek
dc.contributor.authorKuş, Gökhan
dc.contributor.authorÖzkurt, Mete
dc.contributor.authorÖzdemir, Ahmet
dc.contributor.authorKaplancıklı, Zafer Asım
dc.date.accessioned2019-10-19T14:44:46Z
dc.date.available2019-10-19T14:44:46Z
dc.date.issued2016
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.urihttps://dx.doi.org/10.1016/j.ejmech.2016.02.036
dc.identifier.urihttps://hdl.handle.net/11421/13606
dc.descriptionWOS: 000374609000014en_US
dc.descriptionPubMed ID: 26927686en_US
dc.description.abstractIn the current work, new 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine derivatives (1-8) were synthesized via the ring closure reaction of 2-bromoacetophenone derivatives with 4-amino-5-[(5-methoxy-2-methyl-1(4-chlorobenzoyl)-1H-indol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-thione, which was obtained via the solvent-free reaction of indomethacin with thiocarbohydrazide. MTT assay was carried out to determine the cytotoxic effects of the compounds on T98 human glioma cell line. Among these compounds, 3-[5-methoxy-2-methyl-1-(4-chlorobenzoyl)-1H-indole-3-yl)methyl]-6-(4-methylphenyl)-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine (8) was found to be the most effective compound and therefore flow cytometric method was performed to investigate the apoptotic effect of compound 8. The apoptosis stimulating percentages of compound 8 in comparison with the control group at 50 and 100 mu M doses were calculated as 11% and 12%, respectively. Besides, real-time PCR assay was carried out to determine the effects of compound 8 on COX-2, caspase 3, 8 and 9, cytochrome c mRNA levels. According to the real-time PCR analysis, compound 8 reduced COX-2 mRNA levels significantly when compared with the control group, whereas the compound did not cause any significant change in other parameters (Caspase 3, 8, 9, cytochrome c). The docking study suggested that the COX-2 inhibitory effects of compound 8 and indomethacin were similar in the catalytic active site of COX-2. These results indicated that compound 8 showed dose-dependent anticancer activity via the inhibition of COX-2 pathwayen_US
dc.language.isoengen_US
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevieren_US
dc.relation.isversionof10.1016/j.ejmech.2016.02.036en_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectTriazoleen_US
dc.subjectTriazolothiadiazineen_US
dc.subjectGliomaen_US
dc.subjectAnticanceren_US
dc.subjectApoptosisen_US
dc.subjectCox-2en_US
dc.titleIndomethacin based new triazolothiadiazine derivatives: Synthesis, evaluation of their anticancer effects on T98 human glioma cell line related to COX-2 inhibition and docking studiesen_US
dc.typearticleen_US
dc.relation.journalEuropean Journal of Medicinal Chemistryen_US
dc.contributor.departmentAnadolu Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalıen_US
dc.identifier.volume113en_US
dc.identifier.startpage179en_US
dc.identifier.endpage186en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.contributor.institutionauthorSever, Belgin
dc.contributor.institutionauthorAltıntop, Mehlika Dilek
dc.contributor.institutionauthorKuş, Gökhan
dc.contributor.institutionauthorÖzdemir, Ahmet
dc.contributor.institutionauthorKaplancıklı, Zafer Asım


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