Apigenin oxidovanadium(IV) cation interactions. Synthesis, spectral, bovine serum albumin binding, antioxidant and anticancer studies

• Published in: Journal of photochemistry and photobiology. A, Chemistry. Vol. 344; pp. 84 - 100
• Main Authors: Martínez Medina, Juan J., Naso, Luciana G., Pérez, Ana L., Rizzi, Alberto, Okulik, Nora B., Ferrer, Evelina G., Williams, Patricia A.M.
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01.07.2017; Elsevier BV
• Subjects: Acetylacetone; Acetylcysteine; Anticancer properties; Antioxidants; Antitumor activity; Apigenin; Artemia; Binding; Bovine serum albumin; Cancer; Cervical cancer; Coordination compounds; Depletion; Flavonoids; Glutathione; Lungs; Metal complexes; Organic chemicals; Oxidative stress; Oxidovanadim(IV); Reactive oxygen species; Reagents; Serum albumin; Thermal measurement; Toxicity; Tumor cell lines; PBS; GSSG; NBT; Oxidative stress; Bovine serum albumin; Oxidovanadim(IV); DPPH; AAPH; H2DCFDA; MTT; BSA; DMEM; LC50; NAC; Apigenin; FBS; VO(api); PMS; ROS; Apigenin (api); MI; GSH; Cancer
• ISSN: 1010-6030; 1873-2666
• DOI: 10.1016/j.jphotochem.2017.05.007

[Display omitted] •Apigenin interacted wih oxidovanadium(IV) with acetylacetone-like coordination.•Moderate antioxidant and cytotoxic activities against A549 and HeLa cells.•Stress oxidative mechanism of cell-killing.•The complex and the ligand could be transported and stored by bovine serum albumin.•The compounds showed no toxicity against Artemia salina and were not mutagenic. Continuing and expanding our previous work on flavonoid oxidovanadium(IV) (VO) metal complexes as possible anti-cancer agents, the VOapigenin compound was synthesized and characterized. An “acetylacetone-like” coordination through the CO and O moieties of the ligand to the metal center with one apigenin ligand per metal ion was assumed using different spectroscopies and elemental analysis as well as thermal measurements. The vibrational experimental spectrum of VOapigenin was supported by theoretical calculations. According to the structure of the flavonoid it exerted mild antioxidant properties that were enhanced by metal coordination. The compounds showed moderate anticancer activity on lung A549 and cervix HeLa cancer cell lines, displaying an incubation time dependent behavior. Cellular increase of reactive oxygen species (ROS) and glutathione depletion have been measured upon incubation with the compounds. These cell killing activities were reverted when natural antioxidants were incubated with the compounds and the addition of the antioxidant agent N-acetylcysteine generated depletion of the cellular ROS levels. Therefore, a stress oxidative mechanism of action has been assumed. Moreover, the compounds showed no toxicity against Artemia salina and were not mutagenic. Both apigenin and the complex could be transported and stored by bovine serum albumin with similar binding constants and mechanisms than other VOflavonoid complexes.