New manganese(II), iron(II), cobalt(II), nickel(II) and copper(II) saccharinate complexes of 2,6-bis(2-benzimidazolyl)pyridine as potential anticancer agents


Icsel C., YILMAZ V. T. , Aydinlik S., AYGÜN M.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.202, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 202
  • Publication Date: 2020
  • Doi Number: 10.1016/j.ejmech.2020.112535
  • Journal Name: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Anticancer activity, Apoptosis, First row divalent transition metals, Saccharinate, 2,6-Bis(2-benzimidazolyl)pyridine, RAY CRYSTAL-STRUCTURE, LIGAND CU(II) COMPLEXES, DOUBLE-STRAND BREAKS, VITRO DNA-BINDING, CELL-CYCLE, STRUCTURAL-CHARACTERIZATION, ANTIPROLIFERATIVE ACTIVITY, TARGETING MITOCHONDRIA, CYTOTOXIC ACTIVITY, CANCER-CELLS
  • Karadeniz Technical University Affiliated: No

Abstract

New mononuclear complexes [Mn(NO3)(sac)(H2O)(bzimpy)]center dot 2DMF (Mn), [Fe(sac)(2)(H2O)(bzimpy)]center dot 2H(2)O (Fe), [Co(bzimpy)(2)](sac)(2)center dot 2H(2)O (Co), [Ni(bzimpy)(2)](sac)(2)center dot H2O center dot i-PrOH (Ni) and [Cu(sac)(2)(bzimpy)]center dot 3DMF (Cu) (sac = saccharinate and bzimpy = 2,6-bis(2-benzimidazolyl)pyridine) were synthesized and structurally characterized by elemental analysis, UV-Vis, IR, ESI-MS and X-ray diffraction. The anticancer activity of the metal complexes against A549 (lung), MCF-7 (breast), HT29 (colon) cancer cells and MCF10A (normal human breast epithelial) cells was tested and compared with those of cisplatin and bzimpy. The complexes displayed potent cytotoxic activity especially in MCF-7 and A549 cell lines, but they were practically inactive against the normal cells. Mechanistic studies with Mn and Cu complexes on A549 cells indicated that the complexes induced G0/G1 arrest. Both complexes increased intracellular ROS (reactive oxygen species) levels and successfully caused both mitochondrial dysfunction and doublestrand DNA breaks. The up-regulated Bax and down-regulated Bcl-2 expression levels, caspase-3/7 activation and reduced Fas expression indicated that Mn and Cu induced ROS-dependent mitochondria-mediated intrinsic apoptosis in A549 cells. (C) 2020 Elsevier Masson SAS. All rights reserved.