Rutin derivatives as potent AGE inhibitors and its relevance in diabetes complications Glycation,a reversible non-enzymatic reaction of the aldehyde groups of reducing sugars with amino groups of proteins, forming Schiff's bases that undergo rearrangements to stable ketoamines. These ketoamines lead to the formation of advanced glycation end products such as fluorescent and non-fluorescent (Nε-carboxymethyllysine, CML) protein adducts. Under hyperglycemic conditions as the one induced by diabetes, this reaction has been implicated in the appearance of diabetic complications that involved kidney, eye and neuronal tissue damage. Aminoguanidine (AG), a proven in vitro AGEs inhibitor, when it was tested as an anti-diabetic drug in human clinical trials presented important side effects and thereby there is a need for new and improved AGEs inhibitors. The reaction of histone H1 and ADP-ribose is used as a model of glycation since this reaction does not require metal and oxygen and allow us to detect true AGE inhibitors and at the same time discard general antioxidants. The search for AGE inhibitors started with rutin, a common dietary flavonoid that is consumed in fruits, vegetables and plant derived beverages. The derivatives of rutin were used since is known that no dietary rutin is absorbed intact due to gut microflora degradation. Our data showed that 3,4-dihydroxyphenylacetic acid,4-methyl catechol were as powerful inhibitors of fluorescence, crosslinks and the formation of CML and CEL protein adducts as AG. These results suggest an effective natural product AGE inhibitors that might potentially be recommended dietary supplements in the prevention of diabetes complications.