RT info:eu-repo/semantics/article
T1 Role of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N^N)-Donor Ligands Bearing Functionalized Tails
A1 Pérez Arnáiz, Cristina
A1 Leal, Jorge .
A1 Busto Vázquez, Natalia
A1 Carrión, María C. .
A1 Rubio Antolin, Ana Rosa
A1 Ortiz, Imanol .
A1 Barone, Giampaolo
A1 Díaz de Greñu Puertas, Borja
A1 Santolaya, Javier
A1 Leal Villalba, José María
A1 Vaquero Gutiérrez, Mónica
A1 Jalón, Félix A.
A1 Manzano, Blanca R. .
A1 García Ruiz, Begoña
K1 Chemistry, Physical and theoretical
K1 Química física
AB Given the potent anticancer properties of cisdiamminedichloroplatinum(II) and knowing its mode of action, wesynthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, twowith 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 andability to bind to deoxyguanosine monophosphate (dGMP), DNA, andalbumin models. By 1H NMR and UV−vis spectroscopies, circulardichroism, agarose gel electrophoresis, differential scanning calorimetrymeasurements, and density functional theory calculations, we verified thatonly 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 1and 4 exhibit good cytotoxicity against human ovarian carcinoma (HeLa) cell line, whereas 2 and 3 are inactive. Although lungcarcinoma (A549) cells are more resistant to the four platinum complexes than HeLa cells, when the protein concentration in theextracellular 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 interactstrongly with BSA and its cellular uptake is negligible and, on the other hand, that 1 and 4 can interact with BSA only weakly, itscellular uptake being higher by several orders. These results point up the important role of the protein binding features on theirbiological activity and cellular uptake of cis-“PtCl2” derivatives. Our results are valuable in the future rational design of newplatinum complexes with improved biological properties, as they expose the importance not only of their DNA binding abilitiesbut also of additional factors such as protein binding.
PB American Chemical Society
SN 0020-1669
YR 2018
FD 2018-05-21
LK http://hdl.handle.net/10259/4798
UL http://hdl.handle.net/10259/4798
LA eng
NO LaCaixa Foundation (LCF/PR/PR12/11070003), Ministerio deEconomíay Competitividad-FEDER (CTQ2014-58812-C2-2-R, CTQ2014-58812-C2-1-R, and CTQ2015-70371-REDT),Consejeríade Educación−Junta de Castilla y León-FEDER(BU042U16), Spain.
DS Repositorio Institucional de la Universidad de Burgos
RD 22-dic-2024