Synthesis and biological evaluation of novel spiro 6-methoxytetralin-1,3'-pyrrolidine based organoselenocyanates against cadmium-induced oxidative and hepatic damage in mice

Eur J Med Chem. 2010 Aug;45(8):3265-73. doi: 10.1016/j.ejmech.2010.04.001. Epub 2010 Apr 10.

Abstract

A series of novel organoselenocyanate compounds (6a-d) having spiro[tetralin-1,3'-pyrrolidine] moiety were synthesized. The compounds were evaluated for their inhibitory activity against cadmium- (Cd) induced toxicity in Swiss Albino mice. All the compounds (6a-d) inhibited the level of lipid peroxidation (LPO) and upregulated the activity of glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels in treatment group in comparison to the untreated Cd control group. Serum transaminase activities, e.g., alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also significantly lowered in the compound-treated mice. Elongation of the alkyl chain length bearing the selenocyanate (SeCN) active group enhanced the potency of the compounds, 6d being the most active one (6d>6c>6b>6a).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Biomarkers / metabolism
  • Cadmium / toxicity*
  • Cyanates / chemistry*
  • Drug Discovery
  • Female
  • Glutathione / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism
  • Liver / pathology
  • Mice
  • Organ Size / drug effects
  • Organoselenium Compounds / chemical synthesis*
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Oxidative Stress / drug effects*
  • Pyrrolidines / chemistry*
  • Selenium Compounds / chemistry*

Substances

  • Antioxidants
  • Biomarkers
  • Cyanates
  • Organoselenium Compounds
  • Pyrrolidines
  • Selenium Compounds
  • Cadmium
  • selenocyanic acid
  • Glutathione