Design and Biological Evaluation of Palladium(II)–Phosphine–Benzimidazole Complexes as Dual Antioxidant and Antiangiogenic Agents

The present study describes the design, synthesis, and characterization of two novel palladium-(II) complexes incorporating phosphine and benzimidazole ligands, followed by a comprehensive evaluation of their antioxidant and antiangiogenic properties. The complexes were fully characterized using spectroscopic and analytical methods. Antioxidant capacity was investigated through a multiassay approach, including ferrous ion-chelating activity, reducing power, and ABTS^•+ radical cation decolorization. Antiangiogenic activity was evaluated <i>in vivo</i> using the chick chorioallantoic membrane (CAM) assay. Palladium complex 1 exhibited the strongest ferrous ion-chelating ability (71.91% inhibition) and the highest ABTS^•+ scavenging activity (49.79%), while Palladium complex 2 demonstrated superior reducing power (EC₅₀ = 1.06 mg/mL). Both complexes showed strong antiangiogenic effects, with Palladium complex 1 achieving an average inhibition score of 0.90comparable to the positive control (±)-thalidomideand without observable irritation or toxicity. These results indicate that both complexes possess potent biological activities; however, the overall antioxidant and antiangiogenic profile of Palladium complex 1 suggests it may be particularly promising as a redox-modulating agent targeting oxidative stress-induced angiogenesis. To the best of our knowledge, this is the first report of palladium-phosphine-benzimidazole complexes demonstrating such dual activity, highlighting their potential as multifunctional candidates in cancer-related therapeutic research.