RT info:eu-repo/semantics/article
T1 Distinct mechanism of action for antitumoral neutral cyclometalated Pt(II)-complexes bearing antifungal imidazolyl-based drugs
A1 Fernández Pampín, Natalia
A1 Vaquero Gutiérrez, Mónica
A1 Gil Antón, Tania
A1 Espino Ordóñez, Gustavo
A1 Fernández Zoppino, Darío
A1 García Ruiz, Begoña
A1 Busto Vázquez, Natalia
K1 Cyclometalated platinum(II) complexes
K1 Clotrimazole
K1 Bifonazole
K1 Reactive oxygen species (ROS)
K1 Antitumoral
K1 Química inorgánica
K1 Chemistry, Inorganic
K1 Bioquímica
K1 Biochemistry
AB Three neutral Pt(II) complexes containing 1-Methylimidazole and the antifungal imidazolyl drugs Clotrimazole and Bifonazole have been prepared. The general formula of the new derivatives is [Pt(κ2-(C^N)Cl(L)], where C^N stands for ppy = 2-phenylpyridinate, and L = 1-Methylimidazole (MeIm) for [Pt-MeIm]; L = Clotrimazole (CTZ) for [Pt-CTZ] and L = Bifonazole (BFZ) for [Pt-BFZ]). The complexes have been completely characterized in solution and the crystal structures of [Pt-BFZ] and [Pt-CTZ] have been resolved. Complexes [Pt-MeIm] and [Pt-BFZ] present higher cytotoxicity than cisplatin in SW480 (colon adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian cancer) cell lines. [Pt-MeIm] shows the highest accumulation in A549 cells, in agreement with its inability to interact with serum albumin. By contrast, [Pt-CTZ] and [Pt-BFZ] interact with serum proteins, a fact that reduces their bioavailability. The strongest interaction with bovine serum albumin (BSA) is found for [Pt-BFZ], which is the least internalized inside the cells. All the complexes are able to covalently interact with DNA. The most cytotoxic complexes, [Pt-MeIm] and [Pt-BFZ] induce cellular accumulation in G0/G1 and apoptosis by a similar pathway, probably involving a reactive oxygen species (ROS) generation mechanism. [Pt-BFZ] turns out to be the most efficient complex regarding ROS generation and causes mitochondrial membrane depolarization, whereas [Pt-MeIm] induces the opposite effect, hyperpolarization of the mitochondrial membrane. On the contrary, the least cytotoxic complex, [Pt-CTZ] cannot block the cell cycle or generate ROS and the mechanism by which it induces apoptosis could be a different one.
PB Elsevier
SN 0162-0134
YR 2022
FD 2022-01
LK http://hdl.handle.net/10259/6253
UL http://hdl.handle.net/10259/6253
LA eng
NO La Caixa Foundation (LCF/PR/PR12/11070003), Consejería de Educación-Junta de Castilla y León-FEDER (BU042U16-BU305P18), Ministerio de Ciencia, Innovación y Universidades (RTI2018-102040-B-100). M.V. is grateful for the financial support received from the Consejería de Educación-Junta de Castilla y León-FEDER (BU042U16-BU305P18).
DS Repositorio Institucional de la Universidad de Burgos
RD 10-may-2024