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


Saadeh H., Kaddoura R., ELHATY I. A. M., Khasawneh M., Samadi A., Semlali A., ...Daha Fazla

Indian Journal of Heterocyclic Chemistry, cilt.33, sa.4, ss.499-507, 2023 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 33 Sayı: 4
  • Basım Tarihi: 2023
  • Doi Numarası: 10.59467/ijhc.2023.33.499
  • Dergi Adı: Indian Journal of Heterocyclic Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, Chemical Abstracts Core
  • Sayfa Sayıları: ss.499-507
  • Anahtar Kelimeler: Anticancer activity, Apoptosis, Benzimidazole, Piperazines
  • İstanbul Gelişim Üniversitesi Adresli: Evet

Özet

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.