Urea Based Derivatives as Anticancer Agents: Cytotoxicity, GST Inhibition, Molecular Docking, ADME, and Molecular Dynamics Approaches

Abstract The primarily the inhibition effects of four urea derivatives ( 10a – d ) were evaluated against glutathione S‐transferase (GST) enzyme. The IC 50 values of 10a – d molecules were determined to be in the range of 1.69–2.21 µM. Lineweaver‐Burk graphs of 10a – d inhibitor molecules were drawn and the Ki constant of the molecules was calculated to be in the range of 0.54–6.62 µM. The IC 50 value of the ethacrynic acid (INN) was found to be 3.26 µM and the Ki constant was 9.25 µM. The antiproliferative effects of 10a – d molecules were investigated in hepatocellular carcinoma (HepG2) cell lines using MTT assay. Their inhibition concentrations were found to be a 50% decrease in cell viability. The in vitro experimental data for 10a – d molecules were supported by extensive in silico analyses such as molecular docking, molecular dynamics simulation and ADME profiling, and their biological effects were explained at the molecular level.