Novel zinc complexes of a non-steroidal anti-inflammatory drug, niflumic acid: Structural characterization, human-DNA and albumin binding properties

Eur J Med Chem. 2018 Jun 10:153:131-139. doi: 10.1016/j.ejmech.2017.05.009. Epub 2017 May 5.

Abstract

Three novel Zn(II) complexes of NSAID niflumic acid (Hnif) were prepared and studied, namely; [Zn(MeOH)4(nif)2] (1), [Zn(cyclam)(nif)2] (2) and [Zn(nif)2(tmen)] (3), where nif is deprotonated niflumic acid, cyclam is 1,4,8,11-Tetraazacyclotetradecane and tmen is N,N,N',N'-Tetramethylethylenediamine. The complexes have been characterized by infrared spectroscopy, elemental and thermal analysis and single-crystal X-ray structure analysis. All three complexes contain two deprotonated niflumato anions monodentately coordinated via carboxylato groups. Furthermore, fluorescence binding studies of the prepared compounds with human genomic DNA-EB (ethidium bromide) were carried out, which suggest that all complexes are able to bind to DNA via intercalation. Moreover, from the obtained results it followed that complexes 2 and 3 bind to DNA from the tissue with aortic aneurysm (aDNA) and control (cDNA) with a different strength. Additionally, complexes 1-3 exhibit good binding affinity to human serum albumin with high binding constant.

Keywords: Albumin; Binding; DNA; NSAID; Niflumic acid; Zinc complexes.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • DNA / metabolism*
  • Humans
  • Intercalating Agents / chemistry*
  • Intercalating Agents / pharmacology
  • Models, Molecular
  • Niflumic Acid / analogs & derivatives*
  • Niflumic Acid / pharmacology
  • Serum Albumin / metabolism*
  • Zinc / chemistry*
  • Zinc / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Coordination Complexes
  • Intercalating Agents
  • Serum Albumin
  • Niflumic Acid
  • DNA
  • Zinc