Solution chemical properties and anticancer potential of 8-hydroxyquinoline hydrazones and their oxidovanadium(IV) complexes.

We report the synthesis and characterization of a family of benzohydrazones (Ln, n = 1–6) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing different substituents in the para position. Their oxidovanadium(IV) complexes were prepared and compounds with 1:1 and 1:2 metal-to-ligand stoichiometry were obtained. All compounds were characterized by elemental analyses and mass spectrometry as well as FTIR, UV–visible absorption, NMR (ligand precursors) and EPR (complexes) spectroscopies, and by DFT computational methods. Proton dissociation constants, lipophilicity and solubility in aqueous media were determined for all ligand precursors. Complex formation with V(IV)O was evaluated by spectrophotometry for L4 (Me-substituted) and L6 (OH-substituted) and formation constants for mono [VO(HL)]+, [VO(L)] and bis [VO(HL) 2 ], [VO(HL)(L)]−, [VO(L) 2 ]2− complexes were determined. EPR spectroscopy indicates the formation of [VO(HL)]+ and [VO(HL) 2 ], with this latter being the major species at the physiological pH. Noteworthy, the EPR data suggest a different behaviour for L4 and L6, which confirm the results obtained in the solid state. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. All complexes show much higher activity on A-375 (IC 50 < 6.3 μM) than in A-549 cells (IC 50 > 20 μM). Complex 3 (F-substituted) shows the lowest IC 50 on both cell lines and lower than cisplatin (in A-375). Studies identified this compound as the one showing the highest increase in Annexin-V staining, caspase activity and induction of double stranded breaks, corroborating the cytotoxicity results. The mechanism of action of the complexes involves reactive oxygen species (ROS) induced DNA damage, and cell death by apoptosis. Synthesis, solution behaviour, and cytotoxicity of oxidovanadium(IV) complexes bearing 8-hydroxyquinoline benzohydrazide hydrazones. The compounds revealed good cytotoxicity on melanoma (A-375) and lung adenocarcinoma (A-549) cancer cell lines. Production of reactive oxygen species (ROS) with concomitant DNA double stranded break (DSB), caused cell death by apoptosis. [Display omitted] • VIVO forms complexes with versatile 8-hydroxyquinoline-hydrazides. • Formation constants for mono and bis complexes are determined. • Cytotoxicity on melanoma cell line occurs at low micromolar values. • Increase in reactive oxygen species induces DNA damage. • Annexin V and Caspase 3/7 flow cytometry confirm cell death by apoptosis. [ABSTRACT FROM AUTHOR]