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Назив: Impact of aromaticity on anticancer activity of polypyridyl ruthenium(II) complexes: synthesis, structure, DNA/protein binding, lipophilicity and anticancer activity
Аутори: Canovic P.
Rilak, Ana
Radisavljević, Snežana
Bratsos, Ioannis
DEMITRI, Nicola
Mitrovic M.
Zelen I.
Bugarčić Z.
Датум издавања: 2017
Сажетак: © 2017, SBIC. Abstract: With the aim of assessing how the aromaticity of the inert chelating ligand can influence the activity of ruthenium(II) polypyridyl complexes, two new monofunctional ruthenium(II) complexes, [Ru(Cl-Ph-tpy)(phen)Cl]Cl (1) and [Ru(Cl-Ph-tpy)(o-bqdi)Cl]Cl (2) (where Cl-Ph-tpy = 4′-(4-chlorophenyl)-2,2′:6′,2″-terpyridine, phen = 1,10-phenanthroline, o-bqdi = o-benzoquinonediimine), were synthesized. All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV–Vis, 1D and 2D NMR, XRD). Their chemical behavior in aqueous solution was studied by UV–Vis and NMR spectroscopy showing that both compounds are relatively labile leading to the formation of the corresponding aqua species 1a and 2a. 1H NMR spectroscopy studies performed on complexes 1 and 2 demonstrated that after the hydrolysis of the Cl ligand, they are capable to interact with guanine derivatives (i.e., 9-methylguanine (9MeG) and 5′-GMP) through the N7, forming monofunctional adduct. The kinetics and the mechanism of the reaction of complexes 1 and 2 with the biologically more relevant 5′-GMP ligand were studied by UV–Vis spectroscopy. DNA/protein interactions of the complexes have been examined by photophysical studies, which demonstrated a bifunctional binding mode of the complexes with DNA and the complexes strongly quench the fluorescence intensity of bovine serum albumin (BSA) through the mechanism of both static and dynamic quenching. Complexes 1 and 2 strongly induced apoptosis of treated cancer cells with high percentages of apoptotic cells and negligible percentage of necrotic cells. In addition, both ruthenium complexes decreased Bcl-2/Bax ratio causing cytochrome c mitochondrial release, the activation of caspase-3 and induction of apoptosis. Graphical Abstract: [Figure not available: see fulltext.].
URI: https://scidar.kg.ac.rs/handle/123456789/11427
Тип: article
DOI: 10.1007/s00775-017-1479-7
ISSN: 0949-8257
SCOPUS: 2-s2.0-85022209634
Налази се у колекцијама:Faculty of Science, Kragujevac
Institute for Information Technologies, Kragujevac

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