Exploring Anticancer Activities and Structure–Activity Relationships of Binuclear Oxidovanadium(IV) Complexes

Dimeric mixed-ligand oxidovanadium complexes [V 2 O 2 (1,3-pdta)(bpy) 2 ]·9H 2 O ( 1 ) and [V 2 O 2 (1,3-pdta)(phen) 2 ]·6H 2 O ( 2 ) feature a symmetric binuclear structure bridged by 1,3-pdta, which is different from our previous reported asymmetric binuclear complex [V 2 O 2 (edta)(phen) 2 ]·11H 2 O ( 3 ).In this study, a wide range of analytical techniques were carried out to fully characterize the complexes 1 and 2 and further investigate their structural stabilities. Density functional theory calculations of 1 and 2 also suggest that they might have good reactivity with biomolecules as anticancer agents. To assess and screen the antitumor activities of compounds 1–3 together with their four corresponding monomeric complexes [VO(ida)(phen)], [VO(ida)(bpy)], [VO(OH)(phen) 2 ]Cl, and [VO(Hedta)] −, we have performed in vitro experiments with hepatocellular carcinoma HepG2 and SMMC-7721 cell lines by MTT analyses. Complex 2 was found to have the highest inhibitory potency against the growth of HepG2 and SMMC-7721 cells (IC 50 = 2.07 ± 0.72 μM for HepG2; 13.00 ± 3.06 μM for SMMC-7721) compared to other compounds. The structure–activity relationship studies showed that the antitumor effect of compound 2 is higher than that of other compounds. After studying the monomeric compounds of 1–3, their effects were also ranked. Moreover, complex 2 displayed stronger binding affinity toward calf thymus DNA ( K b = 5.71 × 10 4 M –1 ) and cleavage activities than the other complexes ( K b = 1.34 × 10 4 M –1 for 1 and 5.22 × 10 4 M –1 for 3, respectively). We further extended the cellular mechanisms of drug action and found that 2 could block DNA synthesis and cell division of HepG2 and 7721 cells and further induce apoptosis by flow cytometry assays. In short, these results indicate that binuclear oxidovanadium compounds could have potential as simple, effective, and safe antitumor agents.