Oxidative stress protection by manganese complexes of tail-tied aza-scorpiand ligands

J Inorg Biochem. 2016 Oct:163:230-239. doi: 10.1016/j.jinorgbio.2016.04.020. Epub 2016 Apr 16.

Abstract

The Mn2+ coordination chemistry of double scorpiand ligands in which two polyazacyclophane macrocycles have been connected by pyridine, phenanthroline and bipyridine spacers has been studied by potentiometry, paramagnetic NMR and electrochemistry. All ligands show high stability with Mn2+ and the complexes were formed in a wide pH range. DFT calculations support the structures and coordination geometries derived from the study. A remarkable antioxidant activity was evidenced for these systems by the McCord-Fridovich assay and in Escherichiacoli sodAsodB deficient bacterial cells. The three systems were tested as anti-inflammatory drugs in human macrophages measuring the accumulation of cytokines upon lipopolysaccharide (LPS) pro-inflammatory effect. All complexes showed anti-inflammatory effect, being [Mn2L1]4+ the most efficient one.

Keywords: Anti-inflammatory activity; Antioxidant activity; Bacteria; Double polyazamacrocyclic scorpiands; Mn(2+) complexes.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal* / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal* / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Antioxidants* / chemical synthesis
  • Antioxidants* / chemistry
  • Antioxidants* / pharmacology
  • Bacterial Proteins / metabolism*
  • Cell Line, Tumor
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Escherichia coli / enzymology*
  • Humans
  • Macrophages / metabolism*
  • Manganese* / chemistry
  • Manganese* / pharmacology
  • Oxidative Stress / drug effects*
  • Superoxide Dismutase / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Bacterial Proteins
  • Coordination Complexes
  • Manganese
  • SodA protein, Bacteria
  • SodB protein, Bacteria
  • Superoxide Dismutase