Extensive research into platinum-based chemotherapeutics has been underway for decades with ruthenium-based complexes emerging as interesting and potent candidates. Even still, there is no evidence of a single mechanism of action across all synthesized and tested Ru-based complexes, prompting the continuance of research in this field. In addition, the mechanism of action varies according to cell line and/or animal model and is seemingly highly individualized and personalized. In accordance with this, the ruthenium complexes are able to activate specific molecular pathways and interact with certain targets within the cell, sometimes reported simultaneously. In this review, we attempt to give a new perspective on ruthenium complexes’ anti-cancer properties and organize selected results from the past 15 years of research connecting their structure with the reported mechanism of action. These results corroborate the previously reported great potential that ruthenium complexes have on cancer in vitro. In addition, the review provides insight into Ru drugs in their clinical trials and their efficacy against cancer including a historical context on metallodrugs, particularly platinum-based complexes, and their antitumor capability.

The need for a systematic approach in developing new metal-based drugs with dual anticancer-antimicrobial properties is emphasized by the vulnerability of cancer patients to bacterial infections. In this context, a novel organometallic assembly was designed, featuring ruthenium(II) coordination with p-cymene, one chlorido ligand, and a bidentate neutral Schiff base derived from 4-methoxybenzaldehyde and N,N-dimethylethylenediamine. The compound was extensively characterized in both solid-state and solution, employing single crystal X-ray diffraction, nuclear magnetic resonance, infrared, ultraviolet-visible spectroscopy, and density functional theory, alongside Hirshfeld surface analysis. The hydrolysis kinetic was thoroughly investigated, revealing the important role of the chloro-aqua equilibrium in the dynamics of binding with deoxyribonucleic acid and bovine serum albumin. Notably, the aqua species exhibited a pronounced affinity for deoxyribonucleic acid, engaging through electrostatic and hydrogen bonding interactions, while the chloro species demonstrated groove-binding properties. Interaction with albumin revealed distinct binding mechanisms. The aqua species displayed covalent binding, contrasting with the ligand-like van der Waals interactions and hydrogen bonding observed with the chloro specie. Molecular docking studies highlighted site-specific interactions with biomolecular targets. Remarkably, the compound exhibited wide spectrum moderate antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, coupled with low micromolar cytotoxic activity against human colorectal adenocarcinoma cells and significant activity against human leukemic monocyte lymphoma cells. The presented findings encourage further development of this compound, promising avenues for its evolution into a versatile therapeutic agent targeting both infectious diseases and cancer.