Design, synthesis and biological evaluation of novel naphthoquinone-4-aminobenzensulfonamide/carboxamide derivatives as proteasome inhibitors

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dc.contributor.authorUysal, Sirin
dc.contributor.authorSoyer, Zeynep
dc.contributor.authorSaylam, Merve
dc.contributor.authorTarikogullari, Ayse H.
dc.contributor.authorYilmaz, Sinem
dc.contributor.authorKirmizibayrak, Petek Ballar
dc.date.accessioned2021-05-03T20:33:31Z
dc.date.available2021-05-03T20:33:31Z
dc.date.issued2021
dc.departmentEge Üniversitesien_US
dc.description.abstractA series of novel 4-aminobenzensulfonamide/carboxamide derivatives bearing naphthoquinone pharmacophore were designed, sythesized and evaluated for their proteasome inhibitory and anti-proliferative 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, beta 1 subunit), trypsin-like (T-L, beta 2 subunit) and chymotrypsin-like (ChT-L, beta 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 mu 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 mu 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 mu 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 mu M, respectively. Furthermore, molecular modeling studies were carried out for the compounds 13, 14 and 28 to investigate the ligand-enzyme binding interactions. (c) 2020 Elsevier Masson SAS. All rights reserved.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116S300]; Ege UniversityEge University [14ECZ042]en_US
dc.description.sponsorshipThis study was supported by grants from The Scientific and Technological Research Council of Turkey (TUBITAK, 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.identifier.doi10.1016/j.ejmech.2020.112890en_US
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.pmid33039723en_US
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2020.112890
dc.identifier.urihttps://hdl.handle.net/11454/70057
dc.identifier.volume209en_US
dc.identifier.wosWOS:000600418500031en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_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.subjectProteasome inhibitoren_US
dc.subjectAntiproliferative activityen_US
dc.subjectNaphthoquinoneen_US
dc.subjectSulfonamide/carboxamideen_US
dc.subjectMolecular dockingen_US
dc.subjectSynthesisen_US
dc.titleDesign, synthesis and biological evaluation of novel naphthoquinone-4-aminobenzensulfonamide/carboxamide derivatives as proteasome inhibitorsen_US
dc.typeArticleen_US

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