Copper(II) complexes with sparfloxacin and nitrogen-donor heterocyclic ligands: Structure-activity relationship

J Inorg Biochem. 2008 Apr;102(4):910-20. doi: 10.1016/j.jinorgbio.2007.12.011. Epub 2007 Dec 23.

Abstract

Three novel neutral mononuclear copper(II) complexes of the third-generation quinolone antibacterial drug sparfloxacin in the presence of a nitrogen donor heterocyclic ligand 2,2'-bipyridine, 1,10-phenanthroline or 2,2'-dipyridylamine have been prepared and characterized physicochemically and spectroscopically. The resultant complexes are of the type Cu(sparfloxacinato)(N-donor)Cl. Copper(II) is pentacoordinate having a distorted square pyramidal geometry. Molecular modeling calculations have been performed in order to propose the lowest energy model structure of the complexes. The interaction of the complexes with calf-thymus DNA has been investigated with diverse spectroscopic techniques and has shown that the complexes can bind to calf-thymus DNA by the intercalative mode. The antimicrobial activity of the complexes has been tested on three different microorganisms. The Cu(sparfloxacinato)(N-donor)Cl complexes are among the most active ones against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, when compared to the other corresponding copper-quinolone complexes studied by our group and their antimicrobial activity is increased in the order bipyam<bipy=phen. We have also shown that two of the Cu(sparfloxacinato)(N-donor)Cl complexes have decreased the viability of human leukemia cells HL-60 in a time-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Copper / chemistry*
  • Fluoroquinolones / chemistry*
  • Fluoroquinolones / pharmacology
  • HL-60 Cells
  • Heterocyclic Compounds / chemistry*
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Ligands
  • Microbial Sensitivity Tests
  • Nitrogen / chemistry*
  • Spectrum Analysis
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Heterocyclic Compounds
  • Ligands
  • Copper
  • Nitrogen
  • sparfloxacin