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dc.creatorNikolic, Stefan
dc.creatorOpsenica, Dejan
dc.creatorFilipović, Vuk
dc.creatorDojčinović, Biljana
dc.creatorArandelovic, Sandra
dc.creatorRadulovic, Singa
dc.creatorGrgurić-Šipka, Sanja
dc.date.accessioned2019-01-30T17:43:26Z
dc.date.available2019-01-30T17:43:26Z
dc.date.issued2015
dc.identifier.issn0276-7333
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1618
dc.description.abstractTwo p-cymenerutheniumchlorido complexes with thiourea derivative of 7-chloroquinoline (C1) and pyridine-3-imidazole (C2) were synthesized starting from [(eta(6)-p-cymene)RuCl2](2) and corresponding ligands. The structures of complexes were determined with elemental analysis and IR, ESIMS, H-1 and C-13{H-1} NMR, and 2D H-1-N-15 correlation NMR spectroscopy. Cytotoxic activities examined by the MTT assay were performed in five human neoplastic cell lines (HeLa, K562, A549, MDA-MB-231, EA.hy926) and one nontumor human fetal lung fibroblast cell line (MRC-5). Tested complexes exhibited low micromolar activities with IC50 in the range 11.03-56.45 mu M, while ligands L1 and L2 were significantly less active. Complex C1 showed cytoselective activity toward the K562 cell line (IC50 = 11.03 +/- 1.39 mu M) and was 3 times less active against the nontumor MRC-5 cell line. Flow cytometry analysis indicated that complexes C1 and C2 after 24 h treatment caused a concentration-dependent increase of the apoptotic sub-G1 fraction (up to 18.4%), comparable to cis-diamminedichloridoplatinum(II) (cisplatin, CDDP), although without other substantial alterations of the cell cycle. A drug-accumulation and DNA-binding study performed by ICP-MS in the K562 cell line revealed that complex C1 had a high intracellular uptake (1.38 mu g Ru/10 (6) cells), which significantly exceeded the intracellular uptake levels of CDDP (0.29 mu g Pt/10 (6) cells) and C2 (0.08 mu g Ru/10 (6) cells). However, both ruthenium complexes C1 and C2 bind to cellular DNA less efficiently in comparison to CDDP. The structure-activity relationship clearly suggested that introduction of a 7-chloroquinoline moiety in the ruthenium(II)-p-cymene complex significantly contributed to the intracellular uptake of C1 and higher cytotoxicity and cytoselectivity.en
dc.publisherAmerican Chemical Society (ACS)
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172035/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41026/RS//
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/256716/EU//
dc.rightsrestrictedAccess
dc.sourceOrganometallics
dc.titleStrong in Vitro Cytotoxic Potential of New Ruthenium-Cymene Complexesen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractГргурић-Шипка, Сања; Дојчиновић, Биљана; Николиц, Стефан; Опсеница, Дејан; Филиповић, Вук; Aранделовиц, Сандра; Радуловиц, Синга;
dc.citation.volume34
dc.citation.issue14
dc.citation.spage3464
dc.citation.epage3473
dc.citation.other34(14): 3464-3473
dc.citation.rankM21
dc.identifier.doi10.1021/acs.organomet.5b00041
dc.identifier.rcubConv_3377
dc.identifier.scopus2-s2.0-84938099772
dc.identifier.wos000358821800004
dc.type.versionpublishedVersion


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