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dc.creatorPavlović, Marijana
dc.creatorNikolić, Stefan
dc.creatorGligorijević, Nevenka
dc.creatorDojčinović, Biljana
dc.creatorAranđelović, Sandra
dc.creatorGrgurić-Šipka, Sanja
dc.creatorRadulović, Siniša
dc.date.accessioned2019-06-28T14:30:56Z
dc.date.available2019-06-28T14:30:56Z
dc.date.issued2019
dc.identifier.issn0949-8257
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/2963
dc.description.abstractThree new ruthenium(II)-arene complexes with pyrido[2′,3′:5,6]pyrazino[2,3-f][1, 10]phenanthroline (ppf) of general formula: C1 ([(ƞ 6 -benzene)Ru(ppf)Cl]PF 6 , C2 ([(ƞ 6 -toluene)Ru(ppf)Cl]PF 6 ) and C3 ([(ƞ 6 -p-cymene)Ru(ppf)Cl]PF 6 ) have been synthesized. The structures of complexes were determined by elemental analysis, IR, ESI–MS, as well as with 1 H and 13 C NMR spectroscopy. Cytotoxic activity has been evaluated in three different human neoplastic cell lines (A549, A375, LS 174T) and in one human non-tumor cell line (MRC-5), by the MTT assay. Complexes C1–C3 showed IC 50 values in the micromolar range below 100 µM. Complex C3, carrying ƞ 6 -p-cymene as the arene ligand, exhibited cytoselective activity toward human malignant melanoma A375 cells (IC 50 = 15.8 ± 2.7 µM), and has been selected for further analyses of its biological effects. Drug-accumulation study performed in the A375 cells disclosed that C3 possess lower ability of entering the cells compared to cisplatin and distributes approximately equally in the cytosol and membrane/organelle fraction of cells. Investigations in the 3D model of A375 cells, disclosed different effects of the complex C3 and cisplatin on growth of multicellular tumor spheroids (MCTSs). While the size of cisplatin-treated MCTSs decreased with time, MCTSs treated with C3 continued to growth. Differences in structural organization and biological activity of this type of ruthenium(II)-arene complexes versus cisplatin in A375 malignant melanoma cells pointed out their different modes of action, and necessity for further biological studies and optimizations for potential applications.en
dc.publisherSpringer Link
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172035/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41026/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Biological Inorganic Chemistry
dc.subjectAnticancer agents
dc.subjectBiological activity
dc.subjectDNA intercalating ligand
dc.subjectRuthenium(II)–arene complexes
dc.titleNew organoruthenium compounds with pyrido[2′,3′:5,6]pyrazino[2,3-f][1, 10]phenanthroline: synthesis, characterization, cytotoxicity, and investigation of mechanism of actionen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractГлигоријевић, Невенка; Николић, Стефан; Павловић, Маријана; Гргурић-Шипка, Сања; Радуловић, Синиша С.; Aранђеловић, Сандра; Дојчиновић, Биљанa;
dc.citation.volume24
dc.citation.issue2
dc.citation.spage297
dc.citation.epage310
dc.citation.rankM21~
dc.identifier.doi10.1007/s00775-019-01647-4
dc.identifier.scopus2-s2.0-85061718583
dc.identifier.wos000460591600013
dc.type.versionpublishedVersion


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