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.
This research was aimed at finding the cytotoxic potential of the mixed ligand copper(II) complex [Cu(tdp)(phen)](ClO4)—where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)-ethylimino)methyl]phenol, and phen is 1,10-phenanthroline—to two genotypically different breast cancer cells, MCF-7 (p53+ and ER+) and MDA-MB-231 (p53- and ER-). The complex has been already shown to be cytotoxic to ME180 cervical carcinoma cells. The special focus in this study was the induction of cell death by apoptosis and necrosis, and its link with ROS. The treatment brought about nuclear fragmentation, phosphatidylserine externalization, disruption of mitochondrial trans-membrane potential, DNA damage, cell cycle arrest at sub-G1 phase, and increase of ROS generation, followed by apoptotic death of cells during early hours and a late onset of necrosis in the cells surviving the apoptosis. The efficacy of the complex against genotypically different breast cancer cells is attributed to a strong association through p53-mitochondrial redox—cell cycle junction. The ADMET properties and docking of the complex at the active site of Top1 are desirable attributes of a lead molecule for development into a therapeutic. Thus, it is shown that the copper(II)–phenolate complex[Cu(tdp)(phen)]+ offers potential to be developed into a therapeutic for breast cancers in general and ER-negative ones in particular.