Synthesis, DNA and BSA binding, in vitro anti-proliferative and in vivo anti-angiogenic properties of some cobalt(iii) Schiff base complexes

In the recent times metal complexes with dual mechanisms of action, anti-cancer and anti-angiogenic, have gained substantial interest in the field of medicinal chemistry. In the present work, cobalt(iii) complexes containing tetradentate Schiff bases [Co(acacen)(HA)(2)](ClO4) [1], [Co(acacen)(DA)(2)](ClO4) [2], [Co(Ph-acacen)(HA)(2)](ClO4) [3] and [Co(Ph-acacen)(DA)(2)](ClO4) [4] (where acacen: N,N '-bis(acetylacetone)ethylenediamine and Ph-acacen: N,N '-bis(1-phenylbutane-1,3-dione)ethylenediamine, HA: heptylamine and DA: dodecylamine) were synthesised and characterized by elemental analysis, ESI-MS, NMR and IR spectroscopy. The interaction between these cobalt complexes and CT-DNA was investigated by various spectroscopic measurements. The results suggest that complexes containing Ph-acacen Schiff base show strong binding affinity for DNA compared to the corresponding acacen Schiff base-containing complexes. Further, the binding of all the complexes to BSA is strong, as evaluated by UV-visible, fluorescence and circular dichroism spectroscopy. Molecular docking analysis has been performed to obtain more insights into the interaction between bio-molecules (DNA and BSA) and the cobalt complexes. The theoretical results agreed well with the experimental results. The cytotoxic potential of all the cobalt complexes was screened by an in vitro method against A549 and VERO cells. The IC50 values indicate that all the cobalt complexes are as active as cisplatin, the standard drug, against A549 cells but the VERO cells were unaffected even at the highest dose. Various staining techniques such as acridine orange (AO)/ethidium bromide (EB), HOECHST 33248, and Annexin V/6-CFDA and cell cycle analysis of A549 cells revealed that the mode of cell death is apoptosis. All the cobalt complexes showed an inhibitory effect on angiogenesis as revealed by in vivo chicken chorio-allantoic membrane assay.