DNA interaction, molecular docking and biological profile of tetradentate histidine based metallointercalators

Abstract

In the present study, a new series of novel mixed ligand metal complexes with the composition of [ML(His)]Cl [where M=Cu(II), Co(II), Ni(II), and Zn(II); L=(E)-4-((4-chloro-3-nitrobenzylidine)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one; His=L-histidine] have been synthesized and characterized by diverse spectral techniques such as elemental analysis, magnetic susceptibility, molar conductivity measurements, FT IR, UV-Vis., 1H NMR, 13C NMR, EPR and ESI-MS studies. The spectral data suggest that the metal complexes espouse square planar geometry around the central metal ions. The DMSO solution of the metal complexes shows higher molar conductance values which might be due to the electrolytic nature of the complexes. Binding nature of these complexes with calf thymus DNA (CT DNA) has been investigated by electronic absorption titration, viscosity measurements and electrochemical techniques. DNA binding experiments results disclose that the synthesized complexes interact with DNA through intercalative mode. The Kb values clearly signify that the copper complex has more intercalating ability than other complexes. In addition, gel electrophoresis assay demonstrates the ability of the complexes to show oxidative cleavage of pUC18 DNA in the presence of activators. The antimicrobial activity of the synthesized compounds was screened for their biological activity against a set of pathogens. Moreover, the experiments on antioxidant activity show that these complexes exhibit good antioxidant profile. Besides, molecular docking studies have been performed to understand the nature of binding of the compounds with COX-2 enzyme.