@misc{10481/71345,
year = {2021},
url = {http://hdl.handle.net/10481/71345},
abstract = {Despite some limitations such as long-term side effects or the potential presence of intrinsic
or acquired resistance, platinum compounds are key therapeutic components for the treatment of
several solid tumors. To overcome these limitations, maintaining the same efficacy, organometallic
ruthenium(II) compounds have been proposed as a viable alternative to platinum agents as they
have a more favorable toxicity profile and represent an ideal template for both, high-throughput
and rational drug design. To support the preclinical development of bis-phoshino-amine ruthenium
compounds in the treatment of breast cancer, we carried out chemical modifications in the structure
of these derivatives with the aim of designing less toxic and more efficient therapeutic agents. We
report new bis-phoshino-amine ligands and the synthesis of their ruthenium counterparts. The
novel ligands and compounds were fully characterized, water stability analyzed, and their in vitro
cytotoxicity against a panel of tumor cell lines representative of different breast cancer subtypes
was evaluated. The mechanism of action of the lead compound of the series was explored. In vivo
toxicity was also assessed. The results obtained in this article might pave the way for the clinical
development of these compounds in breast cancer therapy},
organization = {Ministerio de Ciencia e Innovación y Agencia Estatal de la Investigación, Spain (Grant Nos. PID2020-117788RB-I00, PID2020-
113661GB-I00, CTQ2017-84131-R and RED2018-102387-T Programa Redes Consolider), and Instituto
de Salud Carlos III grant number PI16/01121. Alberto Ocaña’s lab is supported by the Instituto
de Salud Carlos III (ISCIII, PI19/00808); CRIS Cancer Foundation, ACEPAIN, and Diputación de
Albacete.},
publisher = {MDPI},
keywords = {Breast cancer},
keywords = {Metallodrugs},
keywords = {RAPTA derivatives},
keywords = {Phosphino-amine ligands},
title = {Tuning the Cytotoxicity of Bis-Phosphino-Amines Ruthenium(II) Para-Cymene Complexes for Clinical Development in Breast Cancer},
doi = {10.3390/pharmaceutics13101559},
author = {Domínguez Jurado, Elena and Rodríguez Diéguez, Antonio},
}