Diabetes is an environmental risk factor and is caused by the accumulation of advanced glycation end products (AGEs). Metabolic inhibitors such as 2-amino guanidine, metformin and phenformin are all nucleophilic hydrazino compounds which block the formation of fluorescent AGEs. Efficacy of biguanides metformin and phenformin have also been demonstrated very recently in preventing pancreatic ductal adeno carcinoma (PDAC) and specifically phenformin was five times better drug than metformin: http://clincancerres.aacrjournals.org/ April 25, 2018. Studies by Brownlee et al. (Science 1986) elucidated that glycosylation products in diabetes patients are toxic mediators of macro-and microvascular complications and a monoguanide, 2- aminoguanidine prevented diabetes-induced arterial wall protein cross-linking.  Protein cross-links are also formed spontaneously not only in diabetes individuals but also are formed in aging populations . Our recent studies elucidated the anti glycosylation effect of well established drugs, 2-aminoguanidine, metformin, and phenformin were comparable with the flavonoids present in Okra Seed Extracts (OSE) (ACS Book Chapter 2012,ACS 255 ).The inhibition and anti-glycosylation activity of methylglyoxal-induced modification of human serum albumin and lysozyme by stereo-chemically well-defined OSE was illustrated by SDS-PAGE, fluorescence spectroscopy and changes in protein concentrations via Nano-drop spectrophotometry (2016). . Present studies will describe mechanistic implications of the scavenging effects of an amino acid creatine. An extremely facile microwave-induced organic synthesis of creatine-MGO adducts was achieved and characterized by LC-MS/MS. Our results demonstrated that mono-and bis-adducts of creatine-methyl glyoxal adducts were inhibited successfully.

Diabetes as an environmental risk factor: Detailed mechanistic implications of chemistry and scavenging of methyl glyoxal by the formation of creatine's mono-and bis adducts

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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