Synthesis of a novel radical trapping and carbonyl group trapping anti-AGE agent: a pyridoxamine analogue for inhibiting advanced glycation (AGE) and lipoxidation (ALE) end products

Org Lett. 2003 Jul 24;5(15):2659-62. doi: 10.1021/ol0348147.

Abstract

[structure: see text] Pyridoxamine is known to be an effective inhibitor of both advanced glycation (AGE) and advanced lipoxidation (ALE) end products. The synthesis of a novel multifunctional AGE and ALE inhibitor, 6-dimethylaminopyridoxamine (dmaPM, 11) is described. The 6-dimethylamino substituent increases the radical trapping ability of pyridoxamine's phenolic group. Results obtained during ribose glycations show that both the new dmaPM and a known strong radical trapping agent, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), prevent intermolecular protein cross-linking more effectively than pyridoxamine (PM).

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology
  • Cross-Linking Reagents / chemistry
  • Free Radicals / chemistry
  • Glycation End Products, Advanced / antagonists & inhibitors*
  • Lipid Peroxidation / drug effects*
  • Proteins / chemistry
  • Pyridoxamine / analogs & derivatives
  • Pyridoxamine / chemical synthesis*
  • Pyridoxamine / pharmacology*
  • Ribose / chemistry
  • Spectrometry, Fluorescence / methods

Substances

  • Antioxidants
  • Cross-Linking Reagents
  • Free Radicals
  • Glycation End Products, Advanced
  • Proteins
  • Pyridoxamine
  • Ribose