Hypoxia activated Co(III) complexes as prodrugs may provide with a selective delivery of cytotoxic or antibacterial compounds. Whithin this field sixteen novel Co(III) ternary complexes with the general formula Co(4N)(flav)(ClO4)2, where 4N = tris(2-aminoethyl)amine (tren) or tris(2-pyridylmethyl)amine (tpa) and flav = deprotonated form of differently substituted flavonols have been synthesized, characterized, and their cytotoxicity assayed under both normoxic and hypoxic conditions. Molecular structures of two free flavonols and seven complexes are also reported. In all the complexes the bioligands exhibited the expected (O,O) coordination mode and the complexes showed a slightly distorted octahedral geometry. Cyclic voltammetric studies revealed that both the substituents of the flavonoles and the type of 4N donor ligands had an impact on the reduction potential of the complex. The ones containing tren demonstrated significantly higher stability than the tpa analogues, making these former compounds promising candidates for the development of hypoxia-activated prodrug complexes. Tpa complexes showed higher activity against both selected human cancer cell lines (A549, A431) than their free ligand flavonols, indicating that the anticancer activity of the bioligand can be enhanced upon complexation. However, slight hypoxia-selectivity was found only for a tren complex (11) with moderate cytotoxicity. Novel, multitargeted Co(III) complexes with flavonolate and ancillary 4N donor ligands have been synthesized, characterized and tested against selected human derived cancer cell lines under hypoxic and normoxic conditions. Display omitted •Synthesis of CoIII(4N)(flavonolato)2+ type complexes with flavonoles as bioligands.•Chemical characterization of the novel complexes including X-ray studies.•Dependence of the redox behavior of the complexes on the tripodal tetramine (4N).•Biological assay of the complexes against A549 and A431 cancer cell lines.