New nimesulide derivatives with amide/sulfonamide moieties: Selective COX-2 inhibition and antitumor effects

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dc.authorid0000-0001-5261-1856en_US
dc.authorid0000-0003-0195-3383en_US
dc.authorid0000-0001-8989-8045en_US
dc.authorid0000-0002-1095-1614en_US
dc.authorid0000-0002-1740-4867en_US
dc.authorscopusid55887058500en_US
dc.authorscopusid57203003221en_US
dc.authorscopusid57211689507en_US
dc.authorscopusid36857106000en_US
dc.authorscopusid22136607900en_US
dc.authorwosidABQ-9334-2022en_US
dc.authorwosidAAR-5653-2020en_US
dc.authorwosidGSE-3886-2022en_US
dc.authorwosidA-3237-2016en_US
dc.authorwosidJYY-3927-2024en_US
dc.contributor.authorGüngör, Tuğba
dc.contributor.authorÖzleyen, Adem
dc.contributor.authorYılmaz, Yakup Berkay
dc.contributor.authorSiyah, Pınar
dc.contributor.authorAy, Mehmet
dc.contributor.authorBoyuneğmez Tümer, Tuğba
dc.date.accessioned2024-12-25T06:09:15Z
dc.date.available2024-12-25T06:09:15Z
dc.date.issued2021en_US
dc.departmentEnstitüler, Lisansüstü Eğitim Enstitüsü, Biyomoleküler Bilimler Ana Bilim Dalı
dc.departmentFakülteler, Fen Fakültesi, Kimya Bölümü
dc.departmentFakülteler, Fen Fakültesi, Moleküler Biyoloji ve Genetik Bölümü
dc.description.abstractSeventeen new amide/sulfonamide containing nimesulide derivatives were synthesized and characterized by several spectroscopic techniques and primarily investigated for their inhibitory potential on COX enzymes and other pro-inflammatory factors. Experimental analyses showed that among seventeen compounds, N8 and N10 have remarkable potency and selectivity for the COX-2 enzyme over COX-1 at very low doses as compared to nimesulide. Moreover, both N8 and N10 selectively reduced the Lipopolysaccharide (LPS)-stimulated COX-2 mRNA expression level while the COX-1 level remained stable. Both PGE2 release and nitric oxide production in macrophage cells were significantly suppressed by the N8 and N10 treatment groups. In silico ADME/Tox, molecular docking and molecular dynamics (MD) simulations were also conducted. Additionally, all compounds were also screened in a panel of cancer cell lines for their antiproliferative properties by MTT and SRB assays. Compound N17 exhibited a considerable antiproliferative effect on the colon (IC50: 9.24 μM) and breast (IC50: 11.35 μM) cancer cell lines. N17 exposure for 48 h decreased expression of anti-apoptotic protein BCL-2 and increased the expression of apoptogenic BAX. Besides, the BAX/BCL-2 ratio was increased with visible ultrastructural changes and apoptotic bodies under scanning electron microscopy. In order to investigate the structural and dynamical properties of selected hits on the target structures, multiscale molecular modeling studies are also conducted. Our combined in silico and in vitro results suggest that N8 and N10 could be further developed as potential nonsteroidal anti-inflammatory drugs (NSAIDs), while cytotoxic N17 might be studied as a potential lead compound that could be developed as an anticancer agent.en_US
dc.identifier.citationGüngör, T., Özleyen, A., Yılmaz, Y. B., Siyah, P., Ay, M., Durdağı, S., & Boyuneğmez Tümer, T. (2021). New nimesulide derivatives with amide/sulfonamide moieties: Selective COX-2 inhibition and antitumor effects. European Journal of Medicinal Chemistry, 221, 113566. https://doi.org/10.1016/j.ejmech.2021.113566en_US
dc.identifier.doi10.1016/j.ejmech.2021.113566
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.pmid34077833
dc.identifier.scopus2-s2.0-85107075865
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2021.113566
dc.identifier.urihttps://hdl.handle.net/20.500.12428/6788
dc.identifier.volume221en_US
dc.identifier.wosWOS:000661282500041
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorGüngör, Tuğba
dc.institutionauthorÖzleyen, Adem
dc.institutionauthorYılmaz, Yakup Berkay
dc.institutionauthorAy, Mehmet
dc.institutionauthorBoyuneğmez Tümer, Tuğba
dc.language.isoen
dc.publisherElsevier Masson s.r.l.en_US
dc.relation.ispartofEuropean Journal of Medicinal Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/117Z398
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAmideen_US
dc.subjectAnti-inflammatoryen_US
dc.subjectAnticanceren_US
dc.subjectBinary QSAR modelsen_US
dc.subjectDockingen_US
dc.subjectMD simulationsen_US
dc.subjectNimesulideen_US
dc.subjectSulfonamideen_US
dc.subjectSynthesisen_US
dc.titleNew nimesulide derivatives with amide/sulfonamide moieties: Selective COX-2 inhibition and antitumor effects
dc.typeArticle

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