Structural, biological and computational study of oxamide derivative|СТРУКТУРНА, БИОЛОШКА И РАЧУНСКА ИПИТИВАЊА ДЕРИВАТА ОКСАМИДА

A dicarboxylato-diamide-type compound 2,2'-[(1,2-dioxoethane-1,2--diyl)diimino]dibenzoicacid (H(4)obbz) (1) was synthesized and characterized. The crystal structure of K(2)H(2)obbz center dot 2H(2)O (2) was determined by X-ray diffract-tion analysis. The cytotoxic activities of the compounds were tested against four different cancer cell lines MCF-7, A549, HT-29, HeLa and a human nor-mal cell line MRC-5. The results indicate reasonable dose-dependent cytotox-icity 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, H(4)obbz, induced apoptosis and G0/G1 cell cycle arrest, indicating blockage of DNA synthesis as a possible mechanism that trig-gers apoptosis. Docking and molecular dynamics simulations gave similar res-ponses regarding interactions (binding) between their ligands and chaperon Grp78. The MMGBSA determined Delta G binding energies were in the range from -104 to -140 kJ mol(-1)