Dinuclear Organoruthenium Complexes Exhibiting Antiproliferative Activity through DNA Damage and a Reactive-Oxygen-Species-Mediated Endoplasmic Reticulum Stress Pathway

Subtle ligand modifications on ruthenium arene complexes can lead to different mechanisms of action and result in significant changes in the anticancer efficacy. Herein, four novel dinuclear ruthenium­(II) arene complexes were designed and prepared. In vitro tests indicated that complexes 1–3 displayed moderate antiproliferative activity against the tested cancer cells, while the cytotoxicity of complex 4 is superior or comparable to that of cisplatin. Further studies indicated that complexes 1–4 induce cell death through DNA interaction and a reactive-oxygen-species-mediated endoplasmic reticulum (ER) stress pathway, which is the first example of an organometallic ruthenium­(II) arene complex to induce ER stress as well as DNA interaction. This kind of dinuclear ruthenium­(II) arene complex has unique biological characteristics and is a promising model for new anticancer drug development.