Recently we described a critical role of Artificial Intelligence (AI), a screening tool at an early stage for diabetic retinopathy identifying tiny lesions, hemorrhages, discoloration resulting in blindness (ACS April 2021). A description of the biological significance of metabolic inhibitors metformin, phenformin and a mono- guanide (2-aminoguanidine) as anti-diabetic drugs and their comparison with bioactives present in okra seed extract and bitter melon peel as well as their receptor was elucidated. Present studies describe mechanistic implications of the synergistic effect of sodium oxamate with the anti-diabetic drug metformin. Sodium oxamate, is a lactate dehydrogenase (LDH) inhibitor and has been used with phenformin to reduce the side-effect of lactic acidosis. The nucleophilic metabolic inhibitors biguanide, phenformin and a monoguanidie 2-aminoguanidine are associated with more severe lactic acidosis side effects than metformin and were withdrawn in late1970 for the treatment of diabetes. The present studies describe the nature of the chemical compound formed when metformin was treated with sodium oxamate: Briefly, metformin (20 mg) in 2ml ethanol was mixed with sodium oxamate (30 mg), 200 microliters triethylamine and 200 microliters glacial acetic acid and the mixture microwaved for 50 seconds. The reaction mixture was resolved by analytical and preparative TLC and analyzed via Nanodrop Spectrometer and Electrospray Ionization Mass Spectrometry (ES-API, Neg. Scan exhibited m/z 164 (100 %). A tentative reaction mechanism and molecular weight assignment showed a 7 membered ring (m/z 164 (m/z 182-H2O). These observations will be potentially helpful in explaining recent studies advanced by Rajesh Kumar et al. (AACR April 25, 2018) on the efficacy of biguanides metformin and phenformin preventing pancreatic ductal adenocarcinoma (PDAC) where phenformin was demonstrated five times better drug than metformin.

Mechanistic implications of the synergistic effect of diabetes drug metformin with the lactate dehydrogenase inhibitor sodium oxamate

ACS Spring 2022

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