Design, Synthesis, and Biological Evaluation of Newly Synthesized Cinnamide-Fluorinated Containing Compounds as Bioactive Anticancer Agents.

A new series of cinnamide-fluorinated derivatives has been synthesized and characterized by using different spectroscopic and elemental microanalyses methods. All of the prepared -fluorocinnamide derivatives were evaluated for their cytotoxic activity against the HepG2 liver cancerous cell line. The imidazolone derivative , which bears -(-pyrimidin-2-ylbenzenesulphamoyl) moiety, displayed antiproliferative activity against HepG2 liver cancerous cells with an IC value of 4.23 μM as compared to staurosporin (STU) (IC = 5.59 μM). In addition, compound experienced epidermal growth factor receptor (EGFR) inhibitory activity comparable to palatinib. The cell cycle analysis by flow cytometry indicated that compound arrested the cellular cycle of HepG2 cells at the G1 phase. Additionally, as demonstrated by the fluorescence-activated cell sorting (FACS) technique, compound increased both early and late apoptotic ratios compared to control untreated HepG2 cells. Moreover, imidazolone compound induced apoptosis via the intrinsic apoptotic pathway by decreasing the level of mitochondrial membrane polarization (MMP) compared to untreated HepG2 cells. Therefore, the new -(-pyrimidin-2-ylbenzenesulphamoyl)imidazolone derivative could be considered a potential platform for further optimizing an antitumor agent against hepatocellular carcinoma.