Investigation on DNA/Protein interaction of thiosemicarbazone based octahedral nickel(II) and iron(III) complexes

•Synthesis and characterization of Ni(II) and Fe(III) complexes of 2-acetylpyrzine N-(4)-cyclohexylthiosemicarbazide.•A comparative study towards DNA and protein binding affinity of the complexes.•In silico studies carried out to understand the mechanism of drug interaction•The binding between complexes and DNA occur via intercalative mode. 2-acetylpyrzine N-(4)-cyclohexylthiosemicarbazide (H2L) and its metal complexes of Ni(II) and Fe(III) have been synthesized. The structure of H2L and corresponding metal complexes are proposed based on the elemental analysis, UV-Visible, FT-IR spectroscopy, and Far IR. It is evident by means of single diffraction X-ray crystallography that there is a distortion in the octahedral geometry owing to the two units of ligands surrounding the metal ion. To exploit the medicinal potential of the complex thus synthesized, their chemical interactions with Bovine Serum Albumin and CT-DNA were studied at normal physiological conditions using UV–Visible, fluorescence spectral, and viscosity measurement techniques. The results obtained from these studies revealed that the complexes exhibit high affinity for DNA with an affinity constant of 106 M−1 and show non-covalent intercalation. The binding constant (Ka) was calculated by using UV–Visible titration from which it is inferred that Ni(II) has more affinity toward CT-DNA compared to Fe(III) complex. Also, it is established by that there were no extrinsic agents responsible for the DNA cleavage by the complexes. Also, absorption and fluorescent techniques were incorporated to study the interactivity of NiL2 and FeL2 with bovine serum albumin (BSA). In-silico methods were adapted to evaluate the DNA-complex interactions. The outcome of experimental as well as in-silico studies suggests that the metal complexes intercalate with the CT-DNA molecules. Novel Ni(II) and Fe(III) complexes of cyclohexyl based thiosemicarbazone have been synthesized and evaluated their DNA/protein interactions via experimental and computational. [Display omitted]