@misc{10481/92519,
year = {2024},
month = {1},
url = {https://hdl.handle.net/10481/92519},
abstract = {The modular synthesis of the heteroscorpionate core is explored as a tool for the rapid development of
ruthenium-based therapeutic agents. Starting with a series of structurally diverse alcohol-NN ligands, a family of
heteroscorpionate-based ruthenium derivatives was synthesized, characterized, and evaluated as an alternative
to platinum therapy for breast cancer therapy. In vitro, the antitumoral activity of the novel derivatives was
assessed in a series of breast cancer cell lines using UNICAM-1 and cisplatin as metallodrug control. Through this
approach, a bimetallic heteroscorpionate-based metallodrug (RUSCO-2) was identified as the lead compound of
the series with an IC50 value range as low as 3–5 μM. Notably, RUSCO-2 was found to be highly cytotoxic in
TNBC cell lines, suggesting a mode of action independent of the receptor status of the cells. As a proof of concept
and taking advantage of the luminescent properties of one of the complexes obtained, uptake was monitored in
human breast cancer MCF7 cell lines by fluorescence lifetime imaging microscopy (FLIM) to reveal that the
compound is evenly distributed in the cytoplasm and that the incorporation of the heteroscorpionate ligand
protects it from aqueous processes, conversion in another entity, or the loss of the chloride group. Finally, ROS
studies were conducted, lipophilicity was estimated, the chloride/water exchange was studied, and stability
studies in simulated biological media were carried out to propose structure-activity relationships.},
organization = {Ministerio
de Ciencia e Innovación y Agencia Estatal de la Investigación, Spain
(grants CPP2021-008597, PID2020-117788RB-I00 and RED2022-134287-T funded by MCIN/AEI/10.13039/501100011033)},
organization = {Grants
SBPLY/21/180501/000050 and SBPLY/21/180501/000132 funded by
JCCM and by EU through Fondo Europeo de Desarrollo Regional},
organization = {Grant
2021-GRIN-31240 funded by Universidad de Castilla-La Mancha},
organization = {Instituto de Salud Carlos III (grant number PI16/01121)},
organization = {Instituto de Salud Carlos III (ISCIII,
PI19/00808)},
organization = {ACEPAIN
foundation},
organization = {AFANION},
organization = {Junta de Comunidades
de Castilla-La Mancha for Postdoctoral fellowship (2018/15132)},
organization = {University of Castilla-La Mancha
for Predoctoral fellowship (2020-PREDUCLM-16603)},
publisher = {Elsevier},
keywords = {Heteroscorpionate ligands},
keywords = {TNBC},
keywords = {RAPTA derivatives},
title = {Evaluation of heteroscorpionate ligands as scaffolds for the generation of Ruthenium(II) metallodrugs in breast cancer therapy},
doi = {10.1016/j.jinorgbio.2024.112486},
author = {Domínguez Jurado, Elena and Ripoll, Consuelo and Lara Sanchez, Agustín and Ocaña, Alberto and Vitorica-Yrezabal, Iñigo Javier and Bravo, Iván and Alonso Moreno, Carlos},
}