Nickel-diflunisal complexes: synthesis, characterization, in vitro antioxidant activity and interaction with DNA and albumins

J Inorg Biochem. 2016 Sep:162:9-21. doi: 10.1016/j.jinorgbio.2016.06.003. Epub 2016 Jun 4.

Abstract

The reaction of NiCl2 with the non-steroidal anti-inflammatory drug diflunisal (Hdifl) resulted in the formation of complex [Ni(difl-O)2(MeOH)4], 1. The co-existence of a N,N'-donor heterocyclic ligand 2,2'-dipyridylketone oxime (Hpko), 1,10-phenanthroline (phen), 2,2'-bipyridine (bipy) and 2,2'-bipyridylamine (bipyam) led to the formation of complexes [Ni(difl-O)2(Hpko-N,N')2], 2, [Ni(difl)2(phen)(MeOH)2], 3, [Ni(difl)2(bipy)(MeOH)2], 4 and [Ni(difl-O,O')2(bipyam)], 5, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 1 and 2 were determined by X-ray crystallography. The ability of the complexes to scavenge in vitro 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated; the complexes were more active scavengers than free Hdifl. The interaction of the complexes with serum albumins was investigated by fluorescence emission spectroscopy and the binding constants of the compounds to the albumins were calculated. UV spectroscopy, cyclic voltammetry and viscosity measurements as well as fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were employed so as to monitor the interaction of the compounds with calf-thymus DNA and revealed intercalation as the most possible mode of binding.

Keywords: Albumin-binding; Biological activity; DNA-binding; Diflunisal; Nickel complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives
  • 2,2'-Dipyridyl / chemistry
  • Aminopyridines / chemistry
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Benzothiazoles / antagonists & inhibitors
  • Benzothiazoles / chemistry
  • Binding, Competitive
  • Biphenyl Compounds / antagonists & inhibitors
  • Biphenyl Compounds / chemistry
  • Cattle
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry*
  • Crystallography, X-Ray
  • DNA / chemistry
  • Diflunisal / chemistry*
  • Ethidium / chemistry
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry*
  • Hydroxyl Radical / antagonists & inhibitors
  • Hydroxyl Radical / chemistry
  • Models, Molecular
  • Nickel / chemistry*
  • Phenanthrolines / chemistry
  • Picrates / antagonists & inhibitors
  • Picrates / chemistry
  • Protein Binding
  • Serum Albumin / chemistry
  • Sulfonic Acids / antagonists & inhibitors
  • Sulfonic Acids / chemistry

Substances

  • (2,2'-bipyridyl)-3,3'-diamine
  • 2,2'-dipyridylketone
  • Aminopyridines
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzothiazoles
  • Biphenyl Compounds
  • Coordination Complexes
  • Free Radical Scavengers
  • Phenanthrolines
  • Picrates
  • Serum Albumin
  • Sulfonic Acids
  • 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
  • Hydroxyl Radical
  • 2,2'-Dipyridyl
  • nickel chloride
  • Diflunisal
  • Nickel
  • DNA
  • calf thymus DNA
  • 1,1-diphenyl-2-picrylhydrazyl
  • Ethidium
  • 1,10-phenanthroline