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

Abstract

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.

PDE4 inhibitor Rolipram represses hedgehog signaling via ubiquitin-mediated proteolysis of GLI transcription factors to regress breast cancer

“…To analyze if the cells have undergone necrosis or apoptosis due to 24 hours of rolipram treatment, cells were double stained with Annexin V-FITC and propidium iodide (PI) using BD Pharmingen TM Annexin V: FITC Apoptosis Detection Kit (BD Biosciences, Cat# BD556547) using manufacturer's protocol. The data obtained from BD LSRFortessa TM flow cytometer (RRID:SCR_019600) were analyzed using BD FACSDiva TM 9.0 software 16,17 (RRID:SCR_001456).…”

An Overview of Reactive Oxygen Species Damage Occurring during In Vitro Bovine Oocyte and Embryo Development and the Efficacy of Antioxidant Use to Limit These Adverse Effects

“…Copper then reacts through a Fenton-like reaction, enabling it to generate • OH that is heavily reactive towards biomolecules [129,130]. While the Fenton reaction can induce ROS production from excess Cu, deficiencies in Cu are also attributed to inefficient oxidant removal as it is a cofactor for SOD1/3 [131,132]. Therefore, sufficient levels of Zn are necessary to maintain SOD1/3.…”