Synthesis of novel 6-(4-substituted piperazine-1-yl)-9-(β-dribofuranosyl)purine derivatives, which lead to senescence-induced cell death in liver cancer cells

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buir.contributor.authorGüven, Ebru Bilget
buir.contributor.authorÇetin-Atalay, Rengül
dc.citation.epage3065en_US
dc.citation.issueNumber7en_US
dc.citation.spage3058en_US
dc.citation.volumeNumber55en_US
dc.contributor.authorTunçbilek, M.en_US
dc.contributor.authorGüven, Ebru Bilgeten_US
dc.contributor.authorÖnder, T.en_US
dc.contributor.authorÇetin-Atalay, Rengülen_US
dc.date.accessioned2015-07-28T12:04:51Zen_US
dc.date.available2015-07-28T12:04:51Zen_US
dc.date.issued2012en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.departmentGenetics and Biotechnology Research Center (BİLGEN)en_US
dc.description.abstractNovel purine ribonucleoside analogues (9-13) containing a 4-substituted piperazine in the substituent at N-6 were synthesized and evaluated for their cytotoxicity on Huh7, HepG2, FOCUS, Mahlavu liver, MCF7 breast, and HCT116 colon carcinoma cell lines. The purine nucleoside analogues were analyzed initially by an anticancer drug-screening method based on a sulforhodamine B assay. Two nucleoside derivatives with promising cytotoxic activities (11 and 12) were further analyzed on the hepatoma cells. The N-6-(4-Trifluoromethylphenyl)piperazine analogue 11 displayed the best antitumor activity, with IC50 values between 5.2 and 9.2 mu M. Similar to previously described nucleoside analogues, compound 11 also interferes with cellular ATP reserves, possibly through influencing cellular kinase activities. Furthermore, the novel nucleoside analogue 11 was shown to induce senescence-associated cell death, as demonstrated by the SA beta-gal assay. The senescence-dependent cytotoxic effect of 11 was also confirmed through phosphorylation of the Rb protein by p15(INK4b) overexpression in the presence of this compound.en_US
dc.identifier.doi10.1021/jm3001532en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://hdl.handle.net/11693/13168en_US
dc.language.isoEnglishen_US
dc.publisherACSen_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/jm3001532en_US
dc.source.titleJournal of Medicinal Chemistryen_US
dc.subjectNucleoside analogsen_US
dc.subjectCarcinomaen_US
dc.subjectTherapyen_US
dc.subjectFibroblastsen_US
dc.subjectThiopurinesen_US
dc.subjectHallmarksen_US
dc.titleSynthesis of novel 6-(4-substituted piperazine-1-yl)-9-(β-dribofuranosyl)purine derivatives, which lead to senescence-induced cell death in liver cancer cellsen_US
dc.typeArticleen_US
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