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 IC50 values of 10a-d molecules were determined to be in the range of 1.69-2.21 mu M. 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 mu M. The IC50 value of the ethacrynic acid (INN) was found to be 3.26 mu M and the Ki constant was 9.25 mu M. 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.