Novel azo metal chelates of 3-aminophthalhydrazide derivative: Structural investigation, evaluation of DNA cleavage, anticancer and molecular docking studies

Abstract

Transition bivalent metal ion (Mn, Co, Ni, Cu, and Zn) complexes derived from an azo ligand (HLCU) having 1,3-diketone moiety with 3-aminophthalhydrazide were prepared and characterized by using elemental analyses, ultraviolet–visible, Fourier transform infrared, nuclear magnetic resonance (1H, 13C), electron spin resonance, molar conductivity and magnetic measurement studies. Molar conductivity value indicated the non-electrolytic nature of all complexes. The ligand coordinates with the metal ion as a tridentate pattern and the binding sites are carbonyl oxygen, hydrazo nitrogen and hydroxy oxygen of phthalhydrazide moiety. The fluorescence spectra of the compounds were recorded and the results revealed that ligand have higher emission intensity than metal complexes. The X-ray powder diffraction indicated that the ligand (HLCU) and nickel(II) complex have orthorhombic crystal lattices. The ligand and metal complexes were subjected to DNA cleavage activity on pUC18 plasmid DNA using the gel electrophoresis method. The cobalt(II) complex completely cleaved DNA and other compounds showing higher cleaving activity than the control. The antitumor activity of the compounds was screened using sulforhodamine B assay towards the breast cancer and leukaemia cancer cell lines. Manganese(II), cobalt(II) and nickel(II) complexes have more promising activity, and the IC50 value is < 10 μg/mL against the leukaemia carcinoma cell line, which is equally potent as the positive control (adriamycin). The molecular docking study was used to find the binding mode of ligand and complexes of cobalt(II) and nickel(II) towards the molecular target protein receptor. The binding affinity of these compounds is −9.8, −13.6 and −10.5 kcal/mol respectively. The cobalt(II) complex has a more effective binding nature than the ligand and nickel(II) complex. Drug-likeness character indicates moderate activity of HLCU, and [Co(HLCU)(H2O)3], [Ni(HLCU)H2O] complexes, in agreement with invitro results.