title: Antioxidant and anticancer effects and bioavailability studies of the flavonoid baicalin and its oxidovanadium(IV) complex.
abstract: Based on the known antioxidant effect of flavonoids, baicalin (baic) found in roots of Scutellaria has been selected. Its coordination complex with the oxidovanadium(IV) cation, Na4[VO(baic)2].6H2O (VIVO(baic)), was synthesized at pH9 in ethanol and characterized by physicochemical methods. Spectrophotometric studies at pH9 showed a ligand: metal stoichiometry of 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 aryloxide (ArO-) groups in the equatorial plane of the VO moiety, both in solution and in the solid complex. The antioxidant capacity against superoxide and peroxyl radicals of VIVO(baic) resulted greater than for baicalin and correlated with previous results obtained for other VOflavonoid complexes. The coordination mode produces delocalization of the electron density and the stabilization of the radical formed by interaction with external radicals. The complex and the ligand displayed no toxic (Artemia salina test) and no mutagenic (Ames test) effects. 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, being this effect reversed by pre-incubation of the cells with antioxidants such as vitamins C and E. The addition of NAC (N-acetyl-l-cysteine, a sequestering agent of free radicals) suppresses the anticancer effect, confirming the oxidative stress mechanism. The complex interacted with bovine serum albumin (BSA) with stronger binding than baicalin and the mechanisms involved H bonding and van der Waals interactions.
authors.affiliation: Universidad Nacional del Chaco Austral - Comandante Fernández 755, CP: 3700 Presidencia Roque Sáenz Peña, Chaco, Argentina.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Martínez Medina
authors.affiliation: CEQUINOR, CONICET/UNLP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Bv. 120 N° 1465, 1900 La Plata, Argentina.
authors.forename: Luciana G
authors.initials: LG
authors.lastname: Naso
authors.affiliation: Departamento de Física, Facultad de Bioquímica y Ciencias Biológicas-Universidad Nacional del Litoral, Ciudad Universitaria-Paraje El Pozo, 3000 Santa Fe, Argentina.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Pérez
authors.affiliation: Departamento de Física, Facultad de Bioquímica y Ciencias Biológicas-Universidad Nacional del Litoral, Ciudad Universitaria-Paraje El Pozo, 3000 Santa Fe, Argentina.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rizzi
authors.affiliation: CEQUINOR, CONICET/UNLP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Bv. 120 N° 1465, 1900 La Plata, Argentina.
authors.forename: Evelina G
authors.initials: EG
authors.lastname: Ferrer
authors.affiliation: CEQUINOR, CONICET/UNLP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Bv. 120 N° 1465, 1900 La Plata, Argentina. Electronic address: williams@quimica.unlp.edu.ar.
authors.forename: Patricia A M
authors.initials: PAM
authors.lastname: Williams
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014638:Vanadates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D056831:Coordination Complexes; D005419:Flavonoids; D017382:Reactive Oxygen Species; C038044:baicalin; D014638:Vanadates
keywords: Anticancer; Antioxidant; BSA binding; Baicalin; Oxidovanadium(IV) complex