Benzimidazole - Schiff bases and their complexes: synthesis, anticancer activity and molecular modeling as Aurora kinase inhibitor

Z Naturforsch C J Biosci. 2018 Nov 27;73(11-12):465-478. doi: 10.1515/znc-2018-0010.

Abstract

A new series of Schiff bases containing benzіmidazole moiety 11-17 were synthesized by the reaction of 4-(1H-benzо[d]іmіdazоl-2-yl)anіline (1) with different aromatic aldehydes (4-10) via conventional heating and microwave irradiation methods. The structures of the novel Schiff bases were characterized by using different spectral data. Also, metal complexes 18-21 of compound 13 were synthesized, and their structure was confirmed by spectral measurements (IR, NMR, UV), molar conductivity, magnetic susceptibility and thermo-gravimetric analysis. The novel synthesized ligand 13 and its complexes 18-21 were tested for their in vitro antitumor activities towards breast, liver and lung cancer cell lines. Also, the acute toxicity of the prepared compounds 13 and 18-21 was determined in vivo. The results showed that the newly synthesized compounds 13 and 18-21 exhibited a significant activity against cancer, especially for complex 21, compared to standard drug doxorubicin. The molecular docking of complexes 20 and 21 has been also studied as Aurora kinase inhibitors.

Keywords: Schiff bases; benzimidazole; conventional heating; cytotoxicity; metal complexes; microwave irradiation; molecular docking.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Aurora Kinases / antagonists & inhibitors*
  • Aurora Kinases / metabolism
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Male
  • Mice
  • Molecular Docking Simulation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Schiff Bases / chemistry

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Schiff Bases
  • Aurora Kinases