Ruthenium(II)-Arene Complexes Containing Aryl-Isatin Schiff Bases and Their Effects on Colon Cancer Cell Lines

Colorectal cancer is the third most commonly diagnosed cancer worldwide. Although common treatment options, such as platinum-based chemotherapeutics, initially demonstrate efficacy, their use is limited due to extreme side effects, development of chemoresistance, and a high rate of tumor recurrence. This underscores the need for the development of more effective cancer therapeutics with lower side effects. Recently, ruthenium-based compounds have emerged as promising alternatives, as they exhibit reduced cytotoxicity against healthy cells while selectively gaining cytotoxic properties against cancer cells in hypoxic conditions. In this study, we demonstrate the anticancer activities of isatin Schiff bases, including a series of aryl-isatin Schiff base ruthenium(II)-arene complex derivatives denoted Ru1–3, which exhibit coordination with nitrogen and oxygen donor atoms. Among those, Ru1 complex exhibited cytotoxic activity against SW620, Caco-2, and CCD-18Co cell lines with the IC₅₀ values of 5.36 ± 1.09, 9.64 ± 2.57, and 11.04 ± 4.08, respectively. Ru1 complex exhibited strong binding affinity of 5.14 × 10⁶ M⁻¹, and the DNA interaction studies showed intercalation between complex and DNA. Complex Ru2 was analyzed using x-ray crystallography. This major expansion of ruthenium-based Schiff base complexes highlights the importance of ligand design and demonstrates potent cytotoxic activity against colon cancer cells.