5-Aryl-1-Arylideneamino-1 H-Imidazole-2(3 H)-Thiones: Synthesis and In Vitro Anticancer Evaluation

Molecules. 2021 Mar 18;26(6):1706. doi: 10.3390/molecules26061706.

Abstract

A novel series of N-1 arylidene amino imidazole-2-thiones were synthesized, identified using IR, 1H-NMR, and 13C-NMR spectral data. Cytotoxic effect of the prepared compounds was carried out utilizing three cancer cell lines; MCF-7 breast cancer, HepG2 liver cancer, and HCT-116 colon cancer cell lines. Imidazole derivative 5 was the most potent of all against three cell lines. DNA flow cytometric analysis showed that, imidazoles 4d and 5 exhibit pre-G1 apoptosis and cell cycle arrest at G2/M phase. The results of the VEGFR-2 and B-Raf kinase inhibition assay revealed that compounds 4d and 5 displayed good inhibitory activity compared with reference drug erlotinib.

Keywords: Annexin V; VEGFR-2; apoptosis; cell cycle analysis; cytotoxicity; imidazole; synthesis.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Erlotinib Hydrochloride / pharmacology
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • HCT116 Cells
  • Hep G2 Cells
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Structure-Activity Relationship
  • Thiones / chemical synthesis
  • Thiones / chemistry
  • Thiones / pharmacology
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / chemistry

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Thiones
  • Erlotinib Hydrochloride
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf