Synthesis and pharmacological evaluation of amide conjugates of NSAIDs with L-cysteine ethyl ester, combining potent antiinflammatory and antioxidant properties with significantly reduced gastrointestinal toxicity

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3639-43. doi: 10.1016/j.bmcl.2004.05.025.

Abstract

The synthesis and pharmacological evaluation of a series of amide derivatives of NSAIDs with L-cysteine ethyl ester is described. The novel derivatives are potent antiinflammatory, antioxidant and hypocholesterolemic-hypolipidemic agents, while they demonstrate considerably reduced gastrointestinal toxicity. This molecular modification may offer a general route to safer antiinflammatory agents, potentially suitable for chronic use in conditions such as neurodegenerative disorders.

MeSH terms

  • Amides / adverse effects
  • Amides / chemical synthesis
  • Amides / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / adverse effects
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology*
  • Cholesterol / blood
  • Cholesterol / metabolism
  • Cysteine / analogs & derivatives*
  • Cysteine / chemistry*
  • Drug Evaluation
  • Gastrointestinal Diseases / chemically induced*
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / metabolism
  • Mice
  • Rats
  • Triglycerides / blood
  • Triglycerides / metabolism

Substances

  • Amides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Lipoproteins, LDL
  • Triglycerides
  • ethyl cysteine
  • Cholesterol
  • Cysteine