TY - JOUR AU - Filipović, Ignjat P. AU - Mrkalić, Emina M. AU - Pelosi, Giorgio AU - Kojić, Vesna AU - Jakimov, Dimitar AU - Baskić, Dejan AU - Matović, Zoran D. PY - 2022/02/18 Y2 - 2024/03/29 TI - Structural, biological and computational study of oxamide derivative: Scientific paper JF - Journal of the Serbian Chemical Society JA - J. Serb. Chem. Soc. VL - 87 IS - 5 SE - Organic Chemistry DO - 10.2298/JSC211204114F UR - https://www.shd-pub.org.rs/index.php/JSCS/article/view/11451 SP - 545-559 AB - <p>A dicarboxylato-diamide-type compound 2,2'-[(1,2-dioxoethane-1,2-diyl)diimino]dibenzoic acid (H<sub>4</sub>obbz) (<strong>1</strong>) was synthesized and characterized. The crystal structure of K<sub>2</sub>H<sub>2</sub>obbz·2H<sub>2</sub>O (<strong>2</strong>) 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, H<sub>4</sub>obbz, 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 Δ<em>G</em> binding energies were in the range from –104 to –140 kJ mol<sup>-1</sup>.</p> ER -