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dc.contributor.authorUysal, Şirin
dc.contributor.authorSoyer, Zeynep
dc.contributor.authorSaylam, Merve
dc.contributor.authorTarıkoğulları, Aysel H.
dc.contributor.authorYılmaz, Sinem
dc.contributor.authorKırmızıbayrak, Petek Ballar
dc.date.accessioned2021-02-19T21:20:49Z
dc.date.available2021-02-19T21:20:49Z
dc.date.issued2021
dc.identifier.issn0223-5234
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2020.112890
dc.identifier.urihttps://hdl.handle.net/20.500.12868/703
dc.descriptionPubMed: 33039723en_US
dc.description.abstractA series of novel 4-aminobenzensulfonamide/carboxamide derivatives bearing naphthoquinone pharmacophore were designed, sythesized and evaluated for their proteasome inhibitory and antiproliferative activities against human breast cancer cell line (MCF-7). The structures of the synthesized compounds were confirmed by spectral and elemental analyses. The proteasome inhibitory activity studies were carried out using cell-based assay. The antiproteasomal activity results revealed that most of the compounds exhibited inhibitory activity with different percentages against the caspase-like (C-L, ?1 subunit), trypsin-like (T-L, ?2 subunit) and chymotrypsin-like (ChT-L, ?5 subunit) activities of proteasome. Among the tested compounds, compound 14 bearing 5-chloro-2-pyridyl ring on the nitrogen atom of sulfonamide group is the most active compound in the series and displayed higher inhibition with IC50 values of 9.90 ± 0.61, 44.83 ± 4.23 and 22.27 ± 0.15 ?M against ChT-L, C-L and T-L activities of proteasome compared to the lead compound PI-083 (IC50 = 12.47 ± 0.21, 53.12 ± 2.56 and 26.37 ± 0.5 ?M), respectively. The antiproliferative activity was also determined by MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay in vitro. According to the antiproliferative activity results, all of the compounds exhibited cell growth inhibitory activity in a range of IC50 = 1.72 ± 0.14–20.8 ± 0.5 ?M and compounds 13 and 28 were found to be the most active compounds with IC50 values of 1.79 ± 0.21 and 1.72 ± 0.14 ?M, respectively. Furthermore, molecular modeling studies were carried out for the compounds 13, 14 and 28 to investigate the ligand-enzyme binding interactions. © 2020 Elsevier Masson SASen_US
dc.description.sponsorship116S300 Ege Üniversitesi: 14ECZ042 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAKen_US
dc.description.sponsorshipThis study was supported by grants from The Scientific and Technological Research Council of Turkey (TÜBİTAK, Project Number: 116S300 ) and Ege University (Project Number: 14ECZ042 ). The authors thank also to the Pharmaceutical Sciences Research Centre (FABAL) at Ege University, Faculty of Pharmacy for spectral and elemental analyses of the compounds.en_US
dc.language.isoengen_US
dc.publisherElsevier Masson s.r.l.en_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAntiproliferative activityen_US
dc.subjectMolecular dockingen_US
dc.subjectNaphthoquinoneen_US
dc.subjectProteasome inhibitoren_US
dc.subjectSulfonamide/carboxamideen_US
dc.subjectSynthesisen_US
dc.titleDesign, synthesis and biological evaluation of novel naphthoquinone-4-aminobenzensulfonamide/carboxamide derivatives as proteasome inhibitorsen_US
dc.typearticleen_US
dc.contributor.departmentALKÜen_US
dc.contributor.institutionauthor0-belirlenecek
dc.identifier.doi10.1016/j.ejmech.2020.112890
dc.identifier.volume209en_US
dc.relation.journalEuropean Journal of Medicinal Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


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