Synthesis of Some N-(1H-Benzo[d]imidazol-2-yl)-2-(4-Arylpiperazin-1-yl) acetamides as Anticancer Agents

Haythem Saadeh, Raneem Kaddoura, Ismail El-Haty, Mohammad Khasawneh, Abdelouahid Samadi, Abdelhabib Semlali, Nael Abutaha

Research output: Contribution to journalArticlepeer-review


A series of eight N-(1H-benzo[d]imidazol-2-yl)-2-(4-arylpiperazin-1-yl)acetamides was synthesized as potential anticancer agents. Reacting 2-aminobenzimidazole (1) with 2-chloroacetyl chloride in the presence of the base gave N-(1 H-benzo[d]imidazol-2-yl)-2-chloroacetamide (2) which then reacted with substituted piperazines 3a-h to give the targeted compounds 4a-h. The cytotoxic activity of lung (A549) and liver (HepG2) human cancer cells was assessed using the MTT assay. The results demonstrated that IC50 values of 4b, 4c, 4g, and 4h were 4.8 µM, 13.3 µM, 5.1µM, and 11.5 µM on HepG2 cells, respectively. Similarly, the IC50 values of 4b, 4c, 4g, and 4h were 56.9 µM, 46.6 µM, 53.2 µM, and 59.4 µM on A549 cells after 48 h treatment, respectively. The compounds showed higher anticancer activity against HepG2 cells than A549 cells. Compound 4b and 4g mediated cytotoxicity in HepG2 cells by inducing apoptotic cell death, as revealed by fluorescence microscopy. An in silico study was carried out to study the interactions with the active binding site of different receptors. Vascular endothelial growth factor receptor 2 crystal structures (PDB ID; 4ASD) indicated a strong binding mode of 4g compound (ΔG=-10.28 kcal/mol), corresponding with their cytotoxic activities.

Original languageEnglish
Pages (from-to)499-507
Number of pages9
JournalIndian Journal of Heterocyclic Chemistry
Issue number4
Publication statusPublished - 2023


  • Anticancer activity
  • Apoptosis
  • Benzimidazole
  • Piperazines

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry


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