dc.contributor.author | Uysal, Şirin | |
dc.contributor.author | Soyer, Zeynep | |
dc.contributor.author | Saylam, Merve | |
dc.contributor.author | Tarıkoğulları, Aysel H. | |
dc.contributor.author | Yılmaz, Sinem | |
dc.contributor.author | Kırmızıbayrak, Petek Ballar | |
dc.date.accessioned | 2021-02-19T21:20:49Z | |
dc.date.available | 2021-02-19T21:20:49Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 0223-5234 | |
dc.identifier.uri | https://doi.org/10.1016/j.ejmech.2020.112890 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12868/703 | |
dc.description | PubMed: 33039723 | en_US |
dc.description.abstract | A 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 SAS | en_US |
dc.description.sponsorship | 116S300 Ege Üniversitesi: 14ECZ042 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK | en_US |
dc.description.sponsorship | This 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.iso | eng | en_US |
dc.publisher | Elsevier Masson s.r.l. | en_US |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.subject | Antiproliferative activity | en_US |
dc.subject | Molecular docking | en_US |
dc.subject | Naphthoquinone | en_US |
dc.subject | Proteasome inhibitor | en_US |
dc.subject | Sulfonamide/carboxamide | en_US |
dc.subject | Synthesis | en_US |
dc.title | Design, synthesis and biological evaluation of novel naphthoquinone-4-aminobenzensulfonamide/carboxamide derivatives as proteasome inhibitors | en_US |
dc.type | article | en_US |
dc.contributor.department | ALKÜ | en_US |
dc.contributor.institutionauthor | 0-belirlenecek | |
dc.identifier.doi | 10.1016/j.ejmech.2020.112890 | |
dc.identifier.volume | 209 | en_US |
dc.relation.journal | European Journal of Medicinal Chemistry | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |