Cytotoxic behavior and DNA/BSA binding activity of thiosemicarbazone based Ni(II) complex: bio-physical, molecular docking and DFT study

The molecular structure of Ni(II) complexwas determined by X-ray crystallography. The CT-DNA/BSA interaction of both ligand and complex is reported by using various spectroscopic technique. DFT and molecular docking theoretical approach are used to support the experimental results. Both the compounds exhibit a promising cytotoxic activity when compared to the well-known anticancer drug cisplatin and oxaliplatin. [Display omitted] •Synthesis and characterization of thiosemicarbazone based square planar Ni(II) complex.•Both the compound have a good binding activity with DNA and BSA.•Theoretical DFT calculation used to optimization and supports the experimental.•Molecular dockingof the compounds with BSA and DNA supports the experimental findings.•Anticancer activity on MCF-7 and HEK293 cell lines of the compounds are comparable with cisplatin. The bidentate ligand thiosemicarbazone (H3L) and its Ni(II) complex were synthesized and characterized by single crystal X-ray diffraction and various spectroscopic methods. The Ni(II) complex exhibits almost square planar geometry around the nickel ion, coordinated by two ligands through N & S donor centers. The important structural features of single crystal of the complex are [space group: P-1; a = 11.0594(9) Ǻ; b = 12.2339(9) Ǻ; c = 14.8835(9) Ǻ; α = 110.857(6); β = 91.029(6) and γ = 108.710(7)]. The DFT/TD-DFT simulations have been performed to determine the HOMO-LUMO energy, electronic spectroscopy data, the minimum energy optimized structure and to calculate the reactivity descriptors of the compounds using the B3LYP level of theory. The DFT and NBO analysis based on theoretical investigation helps to locate the MEP surface and bonding mode of the ligand in complex respectively. Different reactivity descriptors establish a correlate between their reactivity and bio-molecular affinity of the molecules. The binding abilities of the compounds with DNA and BSA were within the order of standard DNA and BSA binders. The bio-molecular conformational change as well as interactions of the compounds were monitored by biophysical analyses like; 3D fluorescence, FRET calculations and anisotropy studies with BSA. The potent drug likeness antineoplastic and bio-activity of the H3L and Ni(II) complex were assessed using online software PASS and ADMET. The antiproliferative activity of the compounds was evaluated against the normal human embryonic kidney (HEK293) cells and the human breast carcinoma (MCF-7) cancer cell line. Th