Biophysical study on DNA and BSA binding activity of Cu(II) complex: Synthesis, molecular docking, cytotoxic activity, and theoretical approach

The bidentate (N, O) donor Schiff base, methyl‐4‐(2‐hydroxybenzylidene‐amino) benzoate (HL), was synthesized for the synthesis of CuL2 complex. Their structures were characterized by single crystal X‐ray diffraction and spectroscopic methods. The important structural features of ligand HL are (space group: Pca21; a = 6.1434(7) Å; b = 7.1021(7) Å; c = 28.963(3) Å; α = 90.00°; β = 90.00°, and γ = 90.00°) and of CuL2 are (space group: P21/n; a = 15.763(7) Å; b = 8.1921(5) Å, and c = 20.1955(8) Å; α = 90.00°; β = 96.547(4)°, and γ = 90.00°). The DFT/TD‐DFT studies were performed to evaluate the structure optimization, MEP plot, and electronic spectroscopy data as well as the HOMO‐LUMO energy and also other electronic descriptor properties. The DNA and BSA binding property of both the ligand and complex were studied employing a variety of spectroscopic methods, viscosity experiments, and gel electrophoresis technique. Their biophysical study including 3D fluorescence, FRET calculation, and anisotropy measurements with BSA were studied by spectrofluorometric methods. The molecular docking simulation of the ligand HL and CuL2 was executed with DNA and BSA to observe their different weak and strong binding interactions and to compare their binding aptitude with biomolecules and experimental results. The software “PASS” for drug likeness prediction and “ADMET” for bioactivity were implemented to get an idea about the antineoplastic and bioactivity aspects of HL and CuL2 complex. The anticancer property of the Cu(II) complex was measured by MTT assay against human breast carcinomas (MCF‐7) cancer cell line and as well as normal human embryonic kidney cells (HEK293) and is less toxic and comparable anticancer activity compared to cisplatin and oxaliplatin. The annexin V‐FITC, propidium iodide assay by flow cytometric method, and reactive oxygen species (ROS) production assay by DCFDA were assessed in presence of the HL and CuL2 for their cell death mechanism proceed via either apoptosis or necrosis. In vitro and in silico methodologies have been used to investigate the cytotoxicity behavior of Schiff base and its copper (II) complex. Compared to well‐known anticancer drug cisplatin and oxaliplatin, both the compounds have a promising cytotoxic profile.