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dc.creatorFilipović, Nenad R.
dc.creatorBjelogrlić, Snežana
dc.creatorTodorović, Tamara R.
dc.creatorBlagojević, Vladimir A.
dc.creatorMuller, Christian D.
dc.creatorMarinković, Aleksandar
dc.creatorVujčić, Miroslava
dc.creatorJanović, Barbara
dc.creatorMalešević, Aleksandar
dc.creatorBegović, Nebojša N.
dc.creatorSenćanski, Milan
dc.creatorMinić, Dragica M.
dc.date.accessioned2017-06-10T15:45:07Z
dc.date.available2017-11-07
dc.date.issued2016
dc.identifier.issn2046-2069
dc.identifier.urihttp://dais.sanu.ac.rs/123456789/860
dc.description.abstractA new Ni(II) complex, [Ni(L)(H2O)] (1), with diethyl 3,3'-(2,2'-(1,1'-(pyridine-2,6-diyl)bis(ethan-1-yl-1-ylidene))bis(hydrazin-1-yl-2-ylidene))bis(3-oxopropanoate) ligand (H2L) was synthesized as a potential chemotherapeutic agent. Polidentate ligand was coordinated to Ni(II) NNN-tridentately, in dianionic form, while monodentate water coordination completed square-planar geometry around metal. Structure in the solution was determined by NMR spectroscopy and the same coordination mode was observed in the solid state using IR spectroscopy and further verified by DFT calculations and electrochemical studies. Thermal stability of 1 was determined in both air and nitrogen atmosphere. Anticancer activity of 1 was investigated on acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma (AsPC-1) cell lines. On THP-1 cells 1 induced powerful apoptotic response (ED50 = 10 ± 3 µM), which was revealed to be only partially caspase-dependent, with activation of caspase-8 as the dominant course. This suggested that experimentally validated covalent binding of 1 to DNA is not the only mechanism responsible for programmed cell death. This was supported with experiments on AsPC-1 cells. Although treatment of those cells with 1 resulted in poor apoptotic response, cell cycle changes showed concentration-dependent shifts indicating a dual mechanism of activity. This study also reviews the results of preliminary biological screening, which demonstrates that 1 displays a unique pattern of anticancer activity with at least two mechanisms involved. The authors acknowledge networking support by the COST Action CM1106 StemChem – “Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells”. The work was funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant 172055).en
dc.languageen
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172057/RS//
dc.relationCOST Action CM1106 StemChem – “Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells”
dc.rightsembargoedAccess
dc.sourceRSC Advances
dc.subjectNi(II) complexes
dc.subjectbishydrazone
dc.subjectDNA binding
dc.subjectanticancer activity
dc.titleNi(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro–apoptotic and pro–differentiation induction in human cancerous cell linesen
dc.typearticle
dc.rights.licenseBY-NC-ND
dcterms.abstractТодоровић, Тамара Р.; Јановић, Барбара; Вујчић, Мирослава; Маринковић, Aлександар; Муллер, Цхристиан Д.; Филиповић, Ненад Р.; Бјелогрлић, Снежана; Благојевић, Владимир; Минић, Драгица; Сенћански, Милан; Беговић, Небојша; Малешевић, Aлександар;
dc.citation.spage108726
dc.citation.epage108740
dc.citation.volume110
dc.citation.volume6
dc.identifier.wos000389342800068
dc.identifier.doi10.1039/C6RA24604D
dc.identifier.scopus2-s2.0-84997501324
dc.type.versionacceptedVersion


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