Structural, biological and computational study of oxamide derivative

A dicarboxylato-diamide-type compound 2,2'-[(1,2-dioxoethane-1,2- -diyl)diimino]dibenzoic acid (H4obbz) (1) was synthesized and characterized. The crystal structure of K2H2obbz?2H2O (2) was determined by X-ray diffracttion analysis. The cytotoxic activities of the compounds were tested against four different cancer cell lines MCF-7, A549, HT-29, HeLa and a human normal cell line MRC-5. The results indicate reasonable dose-dependent cytotoxicity of the ligands that show selectivity against the tested carcinoma and healthy cell lines. Flow cytometric analysis and fluorescence microscopy showed that the most active compound, H4obbz, induced apoptosis and G0/G1 cell cycle arrest, indicating blockage of DNA synthesis as a possible mechanism that triggers apoptosis. Docking and molecular dynamics simulations gave similar responses regarding interactions (binding) between their ligands and chaperon Grp78. The MMGBSA determined ?G binding energies were in the range from ?104 to ?140 kJ mol-1.