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

Abstract

A new series of cinnamide-fluorinated derivatives has been synthesized and characterized by using different spectroscopic and elemental microanalyses methods. All of the prepared <i>p</i>-fluorocinnamide derivatives were evaluated for their cytotoxic activity against the HepG2 liver cancerous cell line. The imidazolone derivative <b>6</b>, which bears <i>N</i>-(<i>N</i>-pyrimidin-2-ylbenzenesulphamoyl) moiety, displayed antiproliferative activity against HepG2 liver cancerous cells with an IC₅₀ value of 4.23 μM as compared to staurosporin (STU) (IC₅₀ = 5.59 μM). In addition, compound <b>6</b> experienced epidermal growth factor receptor (EGFR) inhibitory activity comparable to palatinib. The cell cycle analysis by flow cytometry indicated that compound <b>6</b> arrested the cellular cycle of HepG2 cells at the G1 phase. Additionally, as demonstrated by the fluorescence-activated cell sorting (FACS) technique, compound <b>6</b> increased both early and late apoptotic ratios compared to control untreated HepG2 cells. Moreover, imidazolone compound <b>6</b> induced apoptosis via the intrinsic apoptotic pathway by decreasing the level of mitochondrial membrane polarization (MMP) compared to untreated HepG2 cells. Therefore, the new <i>N</i>-(<i>N</i>-pyrimidin-2-ylbenzenesulphamoyl)imidazolone derivative <b>6</b> could be considered a potential platform for further optimizing an antitumor agent against hepatocellular carcinoma.