Antioxidant and Anticancer Activities and Protein Interaction of the Oxidovanadium(IV) Naringin Complex

Abstract

The complex of oxidovanadium(IV) with naringin (Narg) [VO(Narg)2] 8H2O (VONarg) was prepared according to the literature improving the synthetic procedure and physicochemical characterization. In addition, biological activities (cytotoxic, antioxidant, and BSA interaction) were determined. The metal coordinated through the 5-hydroxy and 4-carbonyl groups of rings A and C of naringin, respectively. The antioxidant activity of VONarg, determined in vitro, was higher than those of the flavonoid against superoxide and peroxyl reactive oxygen species (ROS) and DPPH radical. The cytotoxic properties were determined by a MTT assay on adenocarcinoma human alveolar basal epithelial cells (A549). VONarg exerted a 20% decrease in cancer cells viability at 24 h incubation, while naringin and oxidovanadium(IV) cation did not show cytotoxicity. Measurements with the normal HEK293 cell line showed that the inhibitory action of the complex is selective. VONarg generated intracellular reactive oxygen species (ROS), depletion of reduced glutathione and depolarization of mitochondrial membrane potential, typical for apoptotic pathway, producing cell death by oxidative stress mechanism. Moreover, naringin interacted with bovine serum albumin (BSA) through hydrophobic interactions in a spontaneous process, and VONarg showed greater affinity for the protein but can still be transported and delivered by it (Ka 104 L·mol−1 order).

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

“…9. In contrast, naringin 7 and oxidovanadium(IV) cation 34 did not significantly elevate ROS levels, while both VONar 2 7 and Phen 6 induced increments in ROS levels at 24 h incubation. The results are in line with the observations regarding cell viability.…”

“…The solid complex [VO(Narg) 2 ] was formed at a higher pH value, pH = 9. 7 From speciation measurements, at pH = 6, the speciation for the VO/phen system shows the formation of [VO(Phen) 2 (OH)] + as the major species. 23 The species [VO(Phen) 2 (H 2 O)] 2+ is formed at pH = 4.…”

“…The calculated IC 50 values are presented in Table 3 and are compared with those previously reported for the oxidovanadium(IV) cation, 29 naringin and VONarg 2 . 7 The ternary complex demonstrated significantly higher activity compared to the binary complex, with IC 50 values of 48.44 and 4100 M, respectively. This behavior indicates that the replacement of one ligand Narg with a rigid, hydrophobic and planar, N,Nheterocyclic ligand in the complex contributes to enhancing its cytotoxic potential, increasing the lipophilicity and improving cell absorption.…”

“…We compared these activities with those of the ligand, the binary complex and the metal ion, previously reported. 7 Table 2 shows the antioxidant effects of the compounds. The ligand Phen did not display superoxide dismutase (SOD) activity and did not scavenge peroxyl, hydroxyl and DPPH radicals.…”

“…42 Comparatively, the binary complex showed higher K b values than naringin, and these values increased with temperature. 7 The replacement of one naringin ligand with Phen in the ternary complex, led to increased binding at 298 K. However, the strength of the BSA-complex bond is weakened with temperature, resulting in a reduction in the binding constant. Moreover, while naringin and VONarg 2 displayed hydrophobic interactions with BSA (indicated by positive DH and DS values), the ternary complex showed hydrogen bonding and van der Waals interactions.…”