Design, Synthesis, Characterization, DFT, Molecular Docking Studies, and Evaluation of Biological Activity of Benzamidethiourea Derivatives against HepG2 Hepatocellular Carcinoma Cell Lines

Ligands derived from benzamide thiourea were used to generate Cu(II) and Pt(IV) complexes. The compounds were extensively characterized utilizing mass spectrometry techniques, including electrospray ionization (ESI) and electron impact (EI), as well as infrared spectroscopy (IR), UV-Vis spectroscopy, and nuclear magnetic resonance spectroscopy (1H- NMR and 13C-NMR). The complexes’ geometric shapes were examined by various techniques, including molar conductivity, magnetic susceptibility, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). The elemental ratios in the complexes were measured by employing Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES). The ligands functioned as bidentate donors, leading to a metal-ligand ratio of 1:2 (M:L). In addition, the present study included theoretical calculations to evaluate the electrophilic or nucleophilic properties of the compounds, as well as several chemical characteristics such as energy gap, chemical hardness, softness, absolute softness, electronegativity, chemical potential, and electrophilicity index. The molecular physicochemical qualities were evaluated by analyzing the structural parameters of the ligands, including bond length, triangle angle, and tetragonal angle, and comparing them to experimental data. The efficiency of the compounds in preventing cancer growth in HepG2 cell lines was evaluated using the MTT assay. Concurrently, most ligands had a moderate level of effectiveness, while a few complexes showed significant potency. The molecular docking investigation of the [Pt(L1)2Cl2] complex with HepG2 cells demonstrated its ability to selectively attach to proteins (2X39, 3E7G, 3EJ8, 4NOS, and 3QX3). The detection of low binding energy and RMSD values provide further substantiation of this interaction.