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Strong in Vitro Cytotoxic Potential of New Ruthenium-Cymene Complexes
dc.creator | Nikolić, Stefan | |
dc.creator | Opsenica, Dejan | |
dc.creator | Filipović, Vuk | |
dc.creator | Dojčinović, Biljana | |
dc.creator | Arandelovic, Sandra | |
dc.creator | Radulovic, Singa | |
dc.creator | Grgurić-Šipka, Sanja | |
dc.date.accessioned | 2019-01-30T17:43:26Z | |
dc.date.available | 2019-01-30T17:43:26Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0276-7333 | |
dc.identifier.uri | https://cer.ihtm.bg.ac.rs/handle/123456789/1618 | |
dc.description.abstract | Two 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.publisher | American Chemical Society (ACS) | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172035/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41026/RS// | |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/256716/EU// | |
dc.rights | restrictedAccess | |
dc.source | Organometallics | |
dc.title | Strong in Vitro Cytotoxic Potential of New Ruthenium-Cymene Complexes | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Гргурић-Шипка, Сања; Дојчиновић, Биљана; Николиц, Стефан; Опсеница, Дејан; Филиповић, Вук; Aранделовиц, Сандра; Радуловиц, Синга; | |
dc.citation.volume | 34 | |
dc.citation.issue | 14 | |
dc.citation.spage | 3464 | |
dc.citation.epage | 3473 | |
dc.citation.other | 34(14): 3464-3473 | |
dc.citation.rank | M21 | |
dc.identifier.doi | 10.1021/acs.organomet.5b00041 | |
dc.identifier.scopus | 2-s2.0-84938099772 | |
dc.identifier.wos | 000358821800004 | |
dc.type.version | publishedVersion |