Investigation of antitumor potential of Ni(II) complexes with tridentate PNO acylhydrazones of 2-(diphenylphosphino)benzaldehyde and monodentate pseudohalides

J Biol Inorg Chem. 2016 Apr;21(2):145-62. doi: 10.1007/s00775-015-1315-x. Epub 2015 Nov 26.

Abstract

Square-planar azido Ni(II) complex with condensation product of 2-(diphenylphosphino)benzaldehyde and Girard's T reagent was synthesized and its crystal structure was determined. Cytotoxic activity of the azido complex and previously synthesized isothiocyanato, cyanato and chlorido Ni(II) complexes with this ligand was examined on six tumor cell lines (HeLa, A549, K562, MDA-MB-453, MDA-MB-361 and LS-174) and two normal cell line (MRC-5 and BEAS-2B). All the investigated nickel(II) complexes were cytotoxic against all tumor cell lines. The newly synthesized azido complex showed selectivity to HeLa and A549 tumor cell lines compared to the normal cells (for A549 IC50 was similar to that of cisplatin). Azido complex interferes with cell cycle phase distribution of A549 and HeLa cells and possesses nuclease activity towards supercoiled DNA. The observed selectivity of the azido complex for some tumor cell lines can be connected with its strong DNA damaging activity.

Keywords: Cytotoxicity; DNA interactions; Girard’s T reagent; Nickel(II) complexes; Phosphine ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzaldehydes / chemistry*
  • Crystallography, X-Ray
  • Halogens / chemistry*
  • HeLa Cells
  • Humans
  • Hydrazones / chemistry*
  • Microscopy, Fluorescence
  • Nickel / chemistry*
  • Spectrometry, Fluorescence
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet

Substances

  • Antineoplastic Agents
  • Benzaldehydes
  • Halogens
  • Hydrazones
  • Nickel