Synthesis and Structure of Naphthoyl Thiourea-Based Binuclear Ruthenium(II) Arene Complexes: Studies on Anticancer Activity and Apoptotic Mechanism.

Herein, we describe the synthesis, characterization and anticancer activity of ruthenium(II) p-cymene complexes comprising naphthoyl thiourea-based ligands. The synthesized  ruthenium(II) complexes(1-3) were fully characterized by elemental analysis and spectral methods. The structure of complex 2 has been elucidated by employing single crystal X-ray diffraction (SC-XRD), which verifies the two bidentate N^O and N^S coordination of the thiourea ligand to two Ru(II) centres. Further, the complexes have been subjected to stability studies to illustrate their aquation behavior in an aqueous medium. All the complexes have been screened for their anticancer efficacy in Breast (MCF-7), Colon (HT-29), Liver (HepG2) cancerous cells and non-cancerous kidney (Hek-293) cells. Among them, complex 2 with an IC50 concentration of 3.59 ± 0.72 µM exhibits the most potent activity in HT-29 cells, surpassing the positive control, cisplatin.  In addition, AO-EB and Hoechst labelling of all the complexes(1-3) on HT-29 cells reveals morphological alterations such as nuclear fragmentation and chromatin condensation resulting from the death of cancerous cells via apoptosis. Biochemical assays such as reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and flow cytometry strongly confirm the cell death via mitochondrial dysfunction-mediated apoptosis.