||We report the synthesis, characterization and biological screening of new chromone Schiff bases derived from the condensation of three 6-substituted-3-formyl-chromones with pyridoxal (HL1-3) and its Cu(II) complexes [Cu(L1-3)Cl], 1-3. For the 6-methyl derivative, HL2, the (VO)-O-IV-complex [VO(L-2)Cl] (5), as well as ternary Cu and (VO)-O-IV complexes with 1,10-phenanthroline (phen), [Cu(L-2)(phen)Cl] (4) and [VO(L-2)(phen)Cl] (6), were also prepared and evaluated. Their stability in aqueous medium and radical scavenging activity toward DPPH are screened, with [Cu(L-2)(phen)Cl] (4) showing hydrolytic stability and [VO(L-2)(phen)Cl] (6) high radical scavenging activity. Spectroscopic studies establish bovine serum albumin (BSA), a model for HSA, as a potential reversible carrier of [Cu(L-2)(phen)Cl] in blood with K-BC approximate to 10(5) M-1. The cytotoxic activity of a group of compounds is evaluated against a panel of human cancer cell lines of different origin (ovary, cervix, brain and breast) and compared to normal cells. Our results indicate that Cu complexes are more cytotoxic than the ligands but not selective towards cancer cells. The most potent complexes (4 and 6) are further evaluated for their apoptotic potential, induction of reactive oxygen species (ROS) and genotoxicity. Both complexes efficiently triggered cell death through apoptosis as evaluated by DNA morphology and TUNEL assay, increased ROS formation as determined by DCFDA (2 ,7 -dichlorodihydrofluorescein diacetate) analysis, and induced genotoxic damage as visualized via COMET assay in all cancer cells under study. Therefore, 4 and 6 may be potential precursor anticancer molecules, yet they need to be targeted toward cancer cells. [GRAPHICS] .