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dc.creatorRadisavljević, Snežana
dc.creatorBratsos, Ioannis
dc.creatorScheurer, Andreas
dc.creatorKorzekwa, Jana
dc.creatorMasnikosa, Romana
dc.creatorTot, Aleksandar
dc.creatorGligorijević, Nevenka N.
dc.creatorRadulović, Siniša S.
dc.creatorRilak Simović, Ana
dc.date.accessioned2018-10-30T08:04:06Z
dc.date.available2018-10-30T08:04:06Z
dc.date.issued2018
dc.identifier.issn1477-9226 (print)
dc.identifier.issn1477-9234 (electronic)
dc.identifier.urihttp://xlink.rsc.org/?DOI=C8DT02903B
dc.identifier.urihttp://vinar.vin.bg.ac.rs/handle/123456789/7894
dc.description.abstractWith the aim of assessing whether Au(iii) compounds with pincer type ligands might be utilized as potential antitumor agents, three new monofunctional Au(iii) complexes of the general formula [Au(N-N'-N)Cl]Cl-2, where N-N'-N = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (H2LtBu, 1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (Me2LtBu, 2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me-2*L, 3) were synthesized. All complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR) and mass spectrometry (MALDI TOF MS). The chemical behavior of the complexes under physiological conditions was studied by UV-Vis spectroscopy, which showed that all compounds were remarkably stable and that the gold center remained in the 3+ oxidation state. The kinetics and the mechanism of the reaction of complexes 1-3 with guanine derivatives (i.e. guanosine (Guo) and guanosine-5-monophosphate (5-GMP)) and calf thymus DNA (CT DNA) were studied by stopped-flow spectroscopy. The three complexes displayed moderately different rate constants in their reactions with Guo, 5-GMP and CT DNA, which can be explained by the steric hindrance and sigma-donicity of the methyl substituent on the bis-pyrazolylpyridine fragment in complexes 2 and 3. The measured enthalpies and entropies of activation (Delta H-not equal > 0, Delta S-not equal < 0) supported an associative mechanism for the substitution process. The interaction of the newly synthesized complexes 1-3 with CT DNA was investigated by UV-Vis and fluorescence spectroscopy, and also by viscosity measurements, which all indicated that complexes 1-3 bound to CT DNA with moderate binding affinity (K-b = 1.6-5.7 x 10(3) M-1) and stabilized the duplex of CT DNA. Molecular docking indicated that complexes 1-3 interacted with DNA via intercalation. Complex 1 reduced the cell survival of all the investigated cell lines (A549, A375, and LS-174) with IC50 values being up to 20 mu M. We have shown that 1 induced perturbations of the cell cycle and led to apoptosis in human melanoma A375 cells. Complex 1 also affected the level of reactive oxygen species (ROS) in the same cells. However, pre-treatment of A375 cells with NAC (ROS scavenger) reversed the effect of 1 on their survival.en
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172011/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41026/RS//
dc.rightsrestrictedAccess
dc.sourceDalton Transactions
dc.titleNew gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicityen
dc.typearticleen
dc.rights.licenseARR
dcterms.abstractСцхеурер, Aндреас; Глигоријевић, Невенка Н.; Радуловић, Синиша С.; Рилак Симовић, Aна; Масникоса, Романа; Тот, Aлександар; Радисављевић, Снежана; Братсос, Иоаннис; Корзекwа, Јана;
dc.rights.holder© 2018 The Royal Society of Chemistry
dc.citation.volume47
dc.citation.issue38
dc.citation.spage13696
dc.citation.epage13712
dc.identifier.wos000446199500047
dc.identifier.doi10.1039/C8DT02903B
dc.identifier.pmid30209465
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-85054049994


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