2. Academic Validation
  3. Design, synthesis, and cytotoxic screening of novel azole derivatives on hepatocellular carcinoma (HepG2 Cells)

Design, synthesis, and cytotoxic screening of novel azole derivatives on hepatocellular carcinoma (HepG2 Cells)

  • Bioorg Chem. 2020 Aug;101:103995. doi: 10.1016/j.bioorg.2020.103995.
Mohammed K Abdelhameid 1,  Islam Zaki 2,  Manal R Mohammed 3,  Khaled O Mohamed 4
Affiliations

Affiliations

  • 1 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: [email protected].
  • 2 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said, Egypt.
  • 3 Department of Radiation Biology, National Center for Radiation Research and Technology, Cairo, Egypt.
  • 4 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
PMID: 32569897 DOI: 10.1016/j.bioorg.2020.103995
Abstract

Novel azole derivatives 3-30 were designed, synthesized, and screened for their antitumor activity on HepG2 cell line. The cytotoxicity screening demonstrated that imidazolone 8 and triazoles 25 and 29 exhibited more potent cytotoxic activities by 1.21-, 4.75-, and 1.8-fold compared to Sorafenib (SOR). Furthermore, vascular endothelial growth factor receptor-2 (VEGFR-2) Enzyme inhibition assay declared that compounds 25 and 29 had inhibitory activity at the nanomolar concentration. Moreover, the tested compounds exhibited good β-tubulin (TUB) polymerization inhibition percentages. In addition, DNA flow cytometry analysis over HepG2 cells indicated that triazoles 25 and 29 demonstrated arrest at G1 and G2/M phase of the cell cycle and induced apoptotic activity by increasing sub-G1 phase. Finally, mechanistic studies of the proapoptotic activities of compounds 8, 10, 11, 25, and 29 indicated that they induced upregulation of P53, Fas/Fas-ligand, and Bax/Bcl-2 ratio expression that resulted in increasing the active Caspase 3/7 percentages and trigger Apoptosis.

Keywords

Anti-cancer; Apoptosis; Imidazolones; Oxazolones; Protein kinase; Triazoles; Tubulin.

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