Antioxidant and anticancer effects and bioavailability studies of the flavonoid baicalin and the oxidovanadium(IV) complex

JUAN J. MARTÍNEZ MEDINA; LUCIANA G. NASO; ALBERTO RIZZI; EVELINA G. FERRER; PATRICIA A.M. WILLIAMS

Budapest

Congreso; 13th European Biological Inorganic Chemistry (EuroBIC 13); 2016

Hungarian Chemical Society

Based on the known antioxidant effect of flavonoids, in this communication the natural flavonoid baicalin (Baic), found in roots of Scutellaria, has been selected. Its coordination complex with the oxidovanadium(IV) cation Na4[VO(Baic)2].6H2O was synthesized at pH 9 in ethanol and characterized by physicochemical methods (elemental analysis, thermogravimetry and spectroscopies). Spectrophotometric studies at pH 9 showed a ligand: metal stoichiometry 2: 1. By vibrational spectroscopy a coordination mode through the cis 5-OH and 6-OH deprotonated groups is inferred. EPR spectroscopy shows an environment of four ArO- groups in the equatorial plane of V=O moiety. The variation of the antioxidant capacity of baicalin and the complex showed improvements on the power to scavenge superoxide and peroxyl radicals upon coordination. No significant differences on the effects on the hydroxyl and DPPH radicals were found. The antioxidant activities correlated with previous results obtained for other VOflavonoid complexes. It can be determined that the coordination with the phenolate groups of ring A, produces delocalization of the electron density and the stabilization the radical formed by interaction with external radicals. The complex and the ligand displayed no toxic effects (using the Artemia salina test). A LD50 value of 244 µM for the mortality of brine shrimp was measured for VOCl2. The complex improved the ability of the ligand to reduce cell viability of human lung cancer cell lines (A549) generating reactive oxygen species (ROS) in cells. Preincubation of the cells with antioxidants such as vitamins C and E reversed the viability inhibition, inferring an anticancer mechanism by oxidative stress. To confirm this mechanism, cellular ROS were measured in the presence of NAC (N-acetyl-L-cysteine, a sequestering agent of free radicals) and the ROS generation and anticancer effects were not observed. Morphological studies were also performed. Both the complex and baicalin interacted with bovine serum albumin (BSA) and a stronger binding of the complex to the protein was found. Both processes resulted spontaneous with a mechanism involving H bonding and van der Waals interactions.