A very recent report described treatment of pancreatic cancer patient-derived xenograft panel with metabolic inhibitors such as metformin and phenformin demonstrating much better efficacy of a biguanide phenformin 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.<br/>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 flavonoids present in Okra Seed Extracts (OSE) (ACS Book Chapter 2012,ACS 255 ). Specifically, the okra seed water extract had very much enhanced antiglycosylation/inhibitory activity. Furthermore, inhibition and anti-glycosylation activity of methylglyoxal-induced modification of human serum albumin and lysozyme by stereo-chemically well-defined OSE was also illustrated by SDS-PAGE, fluorescence spectroscopy and changes in protein concentrations via Nano-drop spectrophotometry.  Studies on the microwave-induced organic synthesis and LC-MS/MS characterization of curcumin adducts of metformin and phenformin and 2-aminoguanidine were also described (2016-2018). Since curcumin is slightly soluble in water by masking the diketone moiety of curcumin with the nucleophilic metabolic inhibitors its solubility was enhanced. Since phenformin suffers from lactic acidosis side effects is not being used clinically for the treatment of diabetes type-2 patients, the curcumin adducts had enhanced antiglycosylation activity. We believe these compounds may have poetential not only for treatment of diabetes but also for pancreatic ductal adenocarcinoma cancer (PDAC).

Diabetes as an environmental risk factor: Biological significance of metabolic inhibitors and their curcumin adducts

ACS Spring Meeting 2021

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