EVALUATION OF THE ANTICANCER ACTIVITY OF A NOVEL NARINGIN-V(IV)O COORDINATION COMPLEX IN HUMAN LUNG CANCER A549 CELLS

RESTREPO, GONZALO; LUCIANA NASO; PABLO GONZALEZ; EVELINA FERRER; PATRICIA WILLIAMS

Otro; Reunión Anual de Sociedades de Biociencias 2023. SAIC SAB AAFE. AACyTAL; 2023

Coordination complexes of bioactive compounds often display an enhanced pharmacological profile compared to the original compound. Their pharmacological effects are influenced by factors such as the identity and quantity of ligands, the metal atom, its oxidation state, coordination mode, and geometry. Variations in these factors can impact properties such as interaction with specific biomolecules, complex stability, solubility, and bioavailability. In a previous study, we prepared two coordination complexes derived from the glycosylated flavonoid naringin and the oxidovanadium(IV) cation, [VO(Narg)2]·8H2O (VONarg) and [VO(Narg)(Phen)Cl]·3H2O (VONargPh). These complexes exhibited enhanced biological activity when compared to naringin. The aim of this study was to modify the coordination site of the oxidovanadium(IV) cation with the flavonoid and assess its anticancer potential against the A549 lung cancer cell line. Physicochemical analysis revealed that the new complex, synthesized at pH = 12, K2[VO(Narg)(H2O)2]·3H2O, coordinates with naringin through the glycosidic region, in contrast to the initial two complexes, which coordinate through the 5-C-O- and 4-C=O groups. It demonstrated higher solubility in aqueous media and exhibited a notable reduction in cell viability (42 %) at 100 μM after 24 h. These results surpassed the effectiveness of VONarg (20%). Additionally, the treatment led to a 112% increase in the production of reactive oxygen species after 4 h of incubation. Furthermore, the levels of the endogenous antioxidant glutathione decreased by 46%, and the mitochondrial membrane potential reduced 12 % in comparison to the control. Moreover, alterations in cellular morphology indicated a loss of cytoplasm and the formation of apoptotic bodies. These findings collectively point to the potential of this complex as an effective agent against cancer cells by inducing oxidative stress (to which cancer cells are more susceptible) and triggering apoptosis