Statement of the Problem: The discovery of new active and selective anticancer agents, able to reduce the noxious side effects of the chemotherapeutics in clinical use, and able to overcome resistance mechanisms, is the main goal for the research in this field.
Methodology & Theoretical Orientation: We have been developing new of [Ru(η5-C5H5) (2,2′-bipyridine-R)(PPh3)]+ based compounds through structure-activity studies, endowed with specific targeting components to take advantage of the singular characteristics of tumor cells and tissues, such as their permeability to macromolecules and overexpression of several receptors. Thus, when in the structure of our compounds R is a biodegradable and biocompatible polymer and/or a biomolecule recognized by cancer cells, passive and/ or active targeting can be achieved, respectively. Through a wide set of biological assays that involved spectroscopic, imaging and proteomic techniques, we show that this family of ruthenium metallodrugs possess very attractive features.
Conclusion & Significance: These compounds show high cytotoxicity against several cancer cell lines with different degrees of aggressiveness (hormone dependent vs triple negative breast cancer) and strong inhibition of key proteins known for their role in mechanisms of cell resistance. Their targets seem to be the proteins that regulate the microtubule or actin dynamics leading to cell death by apoptosis. In vivo studies in a zebrafish model revealed that the compounds are well tolerated. Thus, in this presentation the potential of new ruthenium (II) compounds for the targeted therapy of metastatic and resistant cancers is disclosed. Cancer is rapidly becoming the top killer in the world.