Structural and biological characterization of anticancer nickel(II) bis(benzimidazole) complex

J Inorg Biochem. 2021 Apr:217:111395. doi: 10.1016/j.jinorgbio.2021.111395. Epub 2021 Feb 12.

Abstract

In the present study, nickel(II) complex with 2-[2-[2-(1H-benzimidazol-2-yl)ethylsulfanyl]ethyl]-1H-benzimidazole (tebb) of formula [Ni(tebb)2](ClO4)2 has been prepared and its structure was proved by X-ray crystallography. The central nickel atom is in deformed octahedral vicinity. Four nitrogen atoms of two ligands form plane of octahedral and sulfur atoms are in apical positions. Perchlorate anions are outside the coordination sphere. The coordination compound was tested for its biological activities in an array of in vitro assays. It was found that the synthesized complex possesses interesting biological activity, which is most likely related to its cell-type related uptake kinetics. The synthesized complex is readily uptaken by malignant MDA-MB-231 and CACO-2 cells with the lowest uptake by healthy Hs27 fibroblasts. The lowest IC50 values were obtained for MDA-MB-231 cells (5.2-12.7 μM), highlighting exceptional differential cytotoxicity (IC50 values for healthy fibroblasts were 38.6-51.5 μM). Furthermore, it was found the complex is capable to cause hydrolytic DNA cleavage, promotes an efficient DNA fragmentation and to trigger an extensive formation of intracellular reactive oxygen species. Overall, current work presents a synthesis of Ni(II) coordination compound with interesting biological behavior and with a promising potential to be further tested in pre-clinical models.

Keywords: Benzimidazole; Biocompatibility; Cytotoxicity; Nickel coordination compound; Reactive oxygen species; X-ray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Cell Line, Tumor
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • DNA / drug effects
  • DNA Cleavage / drug effects
  • DNA Fragmentation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Ligands
  • Nickel / chemistry
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Coordination Complexes
  • Ligands
  • Reactive Oxygen Species
  • Nickel
  • DNA