Anti ACHN potency of novel pyridinium-tagged Schiff base of o-vanillin and its Cu (II)-complex; A combined experimental and computational study

Abstract

Copper (II) complexes have been extensively studied for their possible therapeutic use in many diseases and pathologies. Developing these complexes requires expertise in metal coordination chemistry and the design of the ligand to tune the copper (II) center for optimal biological activity. Taking note, herein we report the synthesis, characterization, and in vitro cytotoxicity activity of the new Copper (II) complex of 3-aminopyridinium iodide tagged Schiff base of ortho-vanillin as the ligand system. After synthesizing, the compounds were well characterized by different spectroscopic tools, and the data obtained confirms the formation of the ligand molecule and its paramagnetic mononuclear square planar Cu (II)-complex in a 1:2 M ratio. To reveal the stability of the synthesized Cu (II) complex, different electronic parameters were calculated using Density Functional Theory (DFT). The stability constant of the Cu-complex obtained from Job's plot supports the formation of a fairly stable complex. In vitro, cytotoxicity activity against the ACHN cell line shows that both compounds are active. However, the Cu (II)-complex is more potent with less IC₅₀ value than the ligand, thus revealing the synergistic effect of the Ligand and the Cu (II) ion in their mode of action towards the ACHN cell line. DNA binding constant value for the Cu-complex confirms a non-covalent stacking mode of interaction between the aromatic choromophore of the Cu-complex and the base pair of the DNA, thus casting off DNA intercalative mode of action of the Cu-complex against the ACHN cell line.