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.
[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).
Culbertson
Sean M
SM
Steacie Institute for Molecular Sciences, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada. sean.culbertson@nrc.ca
Enright
Gary D
GD
Ingold
K U
KU
D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D015227:Lipid Peroxidation / Q000187:drug effects*; D011506:Proteins / Q000737:chemistry; D011733:Pyridoxamine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D012266:Ribose / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods
D000975:Antioxidants; D003432:Cross-Linking Reagents; D005609:Free Radicals; D017127:Glycation End Products, Advanced; D011506:Proteins; D011733:Pyridoxamine; D012266:Ribose