Novel inhibitors of advanced glycation endproducts (part II).

Enhanced formation and accumulation of advanced glycation endproducts (AGEs), have been implicated as a major pathogenesis process leading to diabetic complications, normal aging, atherosclerosis, and Alzheimer's Disease. Several potential drug candidates as AGE inhibitors have been reported recently. The aim of this study was to develop classes of novel inhibitors of glycation, AGE formation, and AGE-crosslinking and to investigate their effects through in vitro chemical and immunochemical assays. A total of 92 compounds were designed and synthesized. The first 63 compounds were reported before. Nearly half of the 29 novel inhibitors reported here are benzoic acid derivatives and related molecules, and found to be potent inhibitors of multistage glycation, AGE formation, and AGE-protein crosslinking. All 29 compounds show some degrees of inhibitory activities as detected by the four assay methods, 9 compounds demonstrated high percent inhibition (PI) in all tests, 30 to 40 times stronger than aminoguanidine. Copyright 2000 Academic Press.