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dc.contributor.authorPérez Arnáiz, Cristina 
dc.contributor.authorLeal, Jorge .
dc.contributor.authorBusto Vázquez, Natalia 
dc.contributor.authorCarrión, María C. .
dc.contributor.authorRubio Antolin, Ana Rosa 
dc.contributor.authorOrtiz, Imanol .
dc.contributor.authorBarone, Giampaolo
dc.contributor.authorDíaz de Greñu Puertas, Borja 
dc.contributor.authorSantolaya, Javier
dc.contributor.authorLeal Villalba, José María 
dc.contributor.authorVaquero Gutiérrez, Mónica 
dc.contributor.authorJalón, Félix A.
dc.contributor.authorManzano, Blanca R. .
dc.contributor.authorGarcía Ruiz, Begoña 
dc.date.accessioned2018-05-21T09:00:51Z
dc.date.available2019-05-21T02:45:07Z
dc.date.issued2018-05-21
dc.identifier.issn0020-1669
dc.identifier.urihttp://hdl.handle.net/10259/4798
dc.description.abstractGiven the potent anticancer properties of cisdiamminedichloroplatinum( II) and knowing its mode of action, we synthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, two with N-substituted pbi ligands (pbiR = 1-R-2-(2-pyridyl)benzimidazole) (namely, 1 and 2) and two more with 4,4′-disubstituted bpy ligands (bpy = 2,2′-bipyridine) (namely, 3 and 4). We explored their cytotoxicity and ability to bind to deoxyguanosine monophosphate (dGMP), DNA, and albumin models. By 1H NMR and UV−vis spectroscopies, circular dichroism, agarose gel electrophoresis, differential scanning calorimetry measurements, and density functional theory calculations, we verified that only 3 can form aquacomplex species after dimethyl sulfoxide solvation; surprisingly, 1, 2, and 3 can bind covalently to DNA, whereas 4 can form a noncovalent complex. Interestingly, only complexes 1 and 4 exhibit good cytotoxicity against human ovarian carcinoma (HeLa) cell line, whereas 2 and 3 are inactive. Although lung carcinoma (A549) cells are more resistant to the four platinum complexes than HeLa cells, when the protein concentration in the extracellular media is lower, the cytotoxicity becomes substantially enhanced. By native electrophoresis of bovine seroalbumin (BSA) and inductively coupled plasma mass spectrometry uptake studies we bear out, on one hand, that 2 and 3 can interact strongly with BSA and its cellular uptake is negligible and, on the other hand, that 1 and 4 can interact with BSA only weakly, its cellular uptake being higher by several orders. These results point up the important role of the protein binding features on their biological activity and cellular uptake of cis-“PtCl2” derivatives. Our results are valuable in the future rational design of new platinum complexes with improved biological properties, as they expose the importance not only of their DNA binding abilities but also of additional factors such as protein binding.en
dc.description.sponsorshipLa Caixa Foundation (LCF/PR/PR12/11070003), Ministerio de Economía y Competitividad-FEDER (CTQ2014-58812-C2-2- R, CTQ2014-58812-C2-1-R, and CTQ2015-70371-REDT), Consejería de Educación−Junta de Castilla y León-FEDER (BU042U16), Spain.en
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publisherAmerican Chemical Societyen
dc.relation.ispartofInorganic chemistry, 2018, V. 57, n 10, p. 6124-6134en
dc.subject.otherChemistry, Physical and theoreticalen
dc.subject.otherQuímica físicaes
dc.titleRole of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N^N)-Donor Ligands Bearing Functionalized Tailsen
dc.typeinfo:eu-repo/semantics/article
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.relation.publisherversionhttp://dx.doi.org/10.1021/acs.inorgchem.8b00713
dc.identifier.doi10.1021/acs.inorgchem.8b00713
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/CTQ2014-58812-C2-2-R
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/CTQ2014-58812-C2-1-R,
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/CTQ2015-70371-REDT
dc.relation.projectIDinfo:eu-repo/grantAgreement/JCyL/BU042U16
dc.relation.projectIDinfo:eu-repo/grantAgreement/FundaciónLaCaixa/LCF/PR/PR12/11070003)
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersionen


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