Tuning the Cytotoxicity of Bis-Phosphino-Amines Ruthenium(II) Para-Cymene Complexes for Clinical Development in Breast Cancer

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.

Novel Anticancer Strategies II

“…BCCT is based on the nuclear reaction that results from boron-10 irradiation with neutrons of the appropriate energy to produce high-energy alpha particles and recoiling lithium-7 nuclei. Domínguez-Jurado et al reported the synthesis of a ruthenium compound, namely Ru3 , that showed cytotoxic activity against breast cancer cells, which might serve as the basis for the design of more active and less toxic antitumoral compounds [ 28 ]. Drug repurposing is an efficient and economical approach to identifying novel therapeutic agents from the existing FDA-approved clinically used drug molecules.…”