Novel inhibitors of advanced glycation endproducts.
A number of natural or synthetic compounds as AGE inhibitors have been proposed, discovered or currently being advanced by others and us. We have identified two new classes of aromatic compounds; aryl- (and heterocyclic) ureido and aryl (and heterocyclic) carboxamido phenoxyisobutyric acids, and benzoic acid derivatives and related compounds, as potential inhibitors of glycation and AGE formation. Some of these novel compounds also showed "AGE-breaking" activities in vitro. Current evidence is that chelation of transition metals and/or trapping or indirect inhibition of formation of reactive carbonyl compounds are involved in the mechanisms of action of these novel AGE inhibitors and breakers. Here, we review the inhibitors of glycation and AGE-breakers published to date and present the results of our in vitro and in vivo investigations on a number of these novel AGE inhibitors. These AGE-inhibitors and AGE-breakers may find therapeutic use in the treatment of diseases that AGE formation and accumulation may be responsible for their pathogenesis such as diabetes, Alzheimer's, rheumatoid arthritis, and atherosclerosis.
Rahbar
Samuel
S
Department of Diabetes, Beckman Research Institute of the City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA. srahbar@coh.org
Figarola
James L
JL
D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012709:Serum Albumin / Q000187:drug effects*; D013329:Structure-Activity Relationship
D001565:Benzoates; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006571:Heterocyclic Compounds; D012709:Serum Albumin