Synthesis and pharmacochemical study of novel polyfunctional molecules combining anti-inflammatory, antioxidant, and hypocholesterolemic properties

Bioorg Med Chem Lett. 2006 Feb 15;16(4):825-9. doi: 10.1016/j.bmcl.2005.11.027. Epub 2005 Nov 23.

Abstract

We have designed and synthesized a series of novel molecules having a residue of a classical NSAID and an antioxidant moiety, both attached through amide bonds to a known nootropic structure, an L-proline, trans-4-hydroxy-L-proline or DL-pipecolinic acid residue. The compounds were found to retain anti-inflammatory and antioxidant activities, to acquire hypocholesterolemic action, and to possess a greatly reduced gastrointestinal toxicity. The novel molecules could find useful applications, among others, in slowing the progression or delaying the onset of neurodegenerative diseases.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anticholesteremic Agents / chemical synthesis
  • Anticholesteremic Agents / chemistry
  • Anticholesteremic Agents / pharmacology
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Arthritis / drug therapy*
  • Cholesterol / blood
  • Disease Models, Animal
  • Drug Design
  • Drug Evaluation, Preclinical
  • Female
  • Inflammation / drug therapy*
  • Pipecolic Acids / chemical synthesis
  • Pipecolic Acids / chemistry
  • Pipecolic Acids / pharmacology*
  • Proline / analogs & derivatives
  • Proline / chemical synthesis
  • Proline / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Structure-Activity Relationship
  • Triglycerides / blood

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticholesteremic Agents
  • Antioxidants
  • Pipecolic Acids
  • Triglycerides
  • Cholesterol
  • Proline