Differential Cytotoxic Activity of a New Cationic Pd(II) Coordination Compound with N4-Tetradentate Hybrid Ligand in Cancer Cell Lines

Objective: Successful cancer treatment still requires the discovery of novel compounds that hold promise for chemotherapeutics. The objective of this study was to examine the effectiveness of a newly synthesized cationic palladium(II) coordination compound that functions via several pathways to provide an efficient therapeutic option for various cancer cells. Materials and Methods: A new cationic palladium(II) coordination compound, [Pd(L)]Cl₂·H₂O, denoted as Complex 1, where the ligand L is the compound 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine), was synthesized and characterized by the attenuated total reflectance (ATR)-fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H NMR), electrospray ionization mass spectrometry (ESI-MS), and carbon-hydrogen-nitrogen (CHN) analyses. The density functional theory (DFT) calculations show the coordination sphere around the metal center in Complex 1 to be made up of tertiary N atoms of the pyridine (py) and benzimidazole (bim) rings completing the square-planar geometry with significant distortion. The anti-growth/cytotoxic activity of the complex was determined using the sulforhodamine B (SRB) and adenosine triphosphate (ATP) viability assays for 24 and 48 h in vitro. The study evaluates the determinations for annexin V-propidium iodide (PI) positivity, mitochondrial membrane potential loss, Bcl-2 protein inactivation, and deoxyribonucleic acid (DNA) damage to investigate the cell death mode and its partial mechanism. Results: Complex 1 caused cytotoxicity in a dose-dependent manner in all the cell lines used, with IC₅₀ values ranging from 2.6-8.8 μM for 48 h. Among the cancer models, colon and breast cancer cell lines underwent cell death by well-described apoptosis through the intrinsic pathway involving the mitochondria. However, the other cell lines did not show such a cell death modality. This implies that differential cell death modes operate based on the cancer type. Conclusion: For the treatment of breast and colon cancers, the complex 1 appears to be a unique, promising complex. Therefore, complex 1 deserves further attention for proof of concept in animal models.