2026-06-18T00:06:12Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/47982026-02-06T12:54:15Zcom_10259_4365com_10259_5086com_10259_2604com_10259_4883col_10259_4366col_10259_4884

00925njm 22002777a 4500 dc Pérez Arnáiz, Cristina author Leal, Jorge . author Busto Vázquez, Natalia author Carrión, María C. . author Rubio Antolin, Ana Rosa author Ortiz, Imanol . author Barone, Giampaolo author Díaz de Greñu Puertas, Borja author Santolaya, Javier author Leal Villalba, José María author Vaquero Gutiérrez, Mónica author Jalón Sotés, Félix Ángel author Manzano, Blanca R. . author García Ruiz, Begoña author 2018-05-21 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. 0020-1669 http://hdl.handle.net/10259/4798 10.1021/acs.inorgchem.8b00713 Role of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N^N)-Donor Ligands Bearing Functionalized Tails