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

Dalal Nasser Binjawhar; Fawziah A Al-Salmi; Maha Ali Alghamdi; Arwa Sultan Alqahtani; Eman Fayad; Rasha Mohammed Saleem; Islam Zaki; Amal Mahmoud Youssef Moustafa

doi:10.1021/acsomega.4c00847

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

ACS Omega. 2024 Apr 10;9(16):18505-18515. doi: 10.1021/acsomega.4c00847. eCollection 2024 Apr 23.

Authors

Dalal Nasser Binjawhar¹, Fawziah A Al-Salmi², Maha Ali Alghamdi³, Arwa Sultan Alqahtani⁴, Eman Fayad³, Rasha Mohammed Saleem⁵, Islam Zaki⁶, Amal Mahmoud Youssef Moustafa⁷

Affiliations

¹ Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
² Biology Department, College of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
³ Department of Biotechnology, College of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁴ Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University(IMSIU), P.O. Box 90950, Riyadh 11623, Saudi Arabia.
⁵ Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha 65431, Saudi Arabia.
⁶ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt.
⁷ Chemistry Department, Faculty of Science, Port Said University, Port Said 42526, Egypt.

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 p-fluorocinnamide derivatives were evaluated for their cytotoxic activity against the HepG2 liver cancerous cell line. The imidazolone derivative 6, which bears N-(N-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 6 experienced epidermal growth factor receptor (EGFR) inhibitory activity comparable to palatinib. The cell cycle analysis by flow cytometry indicated that compound 6 arrested the cellular cycle of HepG2 cells at the G1 phase. Additionally, as demonstrated by the fluorescence-activated cell sorting (FACS) technique, compound 6 increased both early and late apoptotic ratios compared to control untreated HepG2 cells. Moreover, imidazolone compound 6 induced apoptosis via the intrinsic apoptotic pathway by decreasing the level of mitochondrial membrane polarization (MMP) compared to untreated HepG2 cells. Therefore, the new N-(N-pyrimidin-2-ylbenzenesulphamoyl)imidazolone derivative 6 could be considered a potential platform for further optimizing an antitumor agent against hepatocellular carcinoma.