Novel dual inhibitors of calpain and lipid peroxidation

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3825-8. doi: 10.1016/j.bmcl.2004.04.105.

Abstract

A series of molecules with dual inhibitory activities on calpain and lipid peroxidation were synthesized. These hybrid compounds were built on the calpain pharmacophore 2-hydroxytetrahydrofuran linked to a set of antioxidants via a l-leucine linker. Compound 7, the most potent in cellular calpain and lipid peroxidation inhibitions, provided effective protection against glial cell death induced by maitotoxin.

MeSH terms

  • Antioxidants / chemical synthesis*
  • Antioxidants / pharmacology
  • Calpain / antagonists & inhibitors*
  • Calpain / metabolism
  • Cell Death / drug effects*
  • Furans / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Leucine / chemistry
  • Lipid Peroxidation / drug effects*
  • Lipoxygenase Inhibitors / chemical synthesis*
  • Lipoxygenase Inhibitors / pharmacology
  • Neuroglia
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Furans
  • Lipoxygenase Inhibitors
  • Calpain
  • Leucine