2024-03-28T16:52:36Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/47982023-02-07T09:01:27Zcom_10259_4365com_10259_5086com_10259_2604com_10259_4883col_10259_4366col_10259_4884
Pérez Arnáiz, Cristina
Leal, Jorge .
Busto Vázquez, Natalia
Carrión, María C. .
Rubio Antolin, Ana Rosa
Ortiz, Imanol .
Barone, Giampaolo
Díaz de Greñu Puertas, Borja
Santolaya, Javier
Leal Villalba, José María
Vaquero Gutiérrez, Mónica
Jalón, Félix A.
Manzano, Blanca R. .
García Ruiz, Begoña
2018-05-21T09:00:51Z
2019-05-21T02:45:07Z
2018-05-21
0020-1669
http://hdl.handle.net/10259/4798
10.1021/acs.inorgchem.8b00713
Given 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.
La
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.
application/pdf
eng
American Chemical Society
Inorganic chemistry, 2018, V. 57, n 10, p. 6124-6134
http://dx.doi.org/10.1021/acs.inorgchem.8b00713
info:eu-repo/grantAgreement/MINECO/CTQ2014-58812-C2-2-R
info:eu-repo/grantAgreement/MINECO/CTQ2014-58812-C2-1-R,
info:eu-repo/grantAgreement/MINECO/CTQ2015-70371-REDT
info:eu-repo/grantAgreement/JCyL/BU042U16
info:eu-repo/grantAgreement/FundaciónLaCaixa/LCF/PR/PR12/11070003)
Chemistry, Physical and theoretical
Química física
Role of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N^N)-Donor Ligands Bearing Functionalized Tails
info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
info:eu-repo/semantics/openAccess