Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties

Bioorg Med Chem. 2007 Jan 15;15(2):951-61. doi: 10.1016/j.bmc.2006.10.056. Epub 2006 Oct 28.

Abstract

Six novel ibuprofen derivatives and related structures, incorporating a proline moiety and designed for neurodegenerative disorders, are studied. They possess anti-inflammatory properties and three of them inhibited lipoxygenase. One compound was found to inhibit cyclooxygenase (COX)-2 production in spleenocytes from arthritic rats. The HS-containing compounds are potent antioxidants and one of them protected against glutathione loss after cerebral ischemia/reperfusion. They demonstrated lipid-lowering ability and seem to acquire low gastrointestinal toxicity. Acetylcholinesterase inhibitory activity, found in two of these compounds, may be an asset to their actions.

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / enzymology
  • Biphenyl Compounds
  • Blood-Brain Barrier / metabolism
  • Cholesterol / blood
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / pharmacology
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Freund's Adjuvant
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / pathology
  • Glutathione / metabolism
  • Hyperlipidemias / blood
  • Hypoxia-Ischemia, Brain / drug therapy
  • Ibuprofen / analogs & derivatives*
  • Ibuprofen / chemical synthesis*
  • Ibuprofen / pharmacology
  • Lipid Peroxidation / drug effects
  • Lipoxygenase Inhibitors / chemical synthesis
  • Lipoxygenase Inhibitors / pharmacology
  • Mice
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / toxicity
  • Nootropic Agents / chemical synthesis*
  • Nootropic Agents / pharmacology*
  • Nootropic Agents / toxicity
  • Oxidative Stress / drug effects
  • Picrates / antagonists & inhibitors
  • Picrates / toxicity
  • Rats
  • Spleen / cytology
  • Spleen / enzymology
  • Triglycerides / blood

Substances

  • Antioxidants
  • Biphenyl Compounds
  • Cholinesterase Inhibitors
  • Cyclooxygenase 2 Inhibitors
  • Lipoxygenase Inhibitors
  • Neuroprotective Agents
  • Nootropic Agents
  • Picrates
  • Triglycerides
  • Freund's Adjuvant
  • Cholesterol
  • 1,1-diphenyl-2-picrylhydrazyl
  • Glutathione
  • Ibuprofen