Influence of the secondary ligand, phenanthroline, on the antioxidant and pro-oxidant and cytotoxic effects of the oxidovanadium(iv)/naringin complex

Abstract

The complex [VONargPhenCl] (Narg, naringin; phen = 1,10-phenanthroline) was synthesized and characterized. Comparative analysis with the binary complex, [VO(Narg)₂], revealed improvements in both antioxidant and anticancer effects upon replacing one Narg ligand with Phen. The new complex behaved as a better antioxidant against reactive oxygen species (ROS) and displayed higher cytotoxicity (against the A549 human lung cancer cell line, 24 h incubation) compared to the ligands and the binary complex. This increased cytotoxic effect was associated with intracellular ROS generation and GSH/GSSG depletion, indicating an oxidative stress mechanism. Additional observations, such as the depletion of mitochondrial membrane potential and morphological changes, suggested the involvement of an intrinsic apoptotic pathway. Furthermore, the complex exhibited enhanced cellular uptake of vanadium compared to the binary complex. The complex demonstrated spontaneous interaction with bovine serum albumin and the binding constant values indicated its ability to be transported by this protein. This study underscores the significance of incorporating a compound with π-electronic delocalization into the coordination sphere of the oxidovanadium(IV) cation that improves the antioxidant capacity. Moreover, its lipophilic characteristics impart an improved transport across the cellular membrane and enhance the pro-oxidant effects in cancer cells, ultimately enhancing the anticancer actions of the metal complex.