Original ArticlesReaction of metformin with dicarbonyl compounds. possible implication in the inhibition of advanced glycation end product formation
Section snippets
Materials
Methylglyoxal and globulin-free BSA were purchased from Sigma. Glyoxal and 3-amino-1,2,4-triazine were purchased from Aldrich. Metformin was obtained from Lipha S.A.
Chemical synthesis of triazepinone
Methylglyoxal (0.21 mol; 34 mL of a 40% aqueous solution) was added between 0° and +5° to a solution of 0.2 mol of N,N-dimethylbiguanide base in 100 mL of water. The reaction mixture was stirred for 1 hr at 5° and for a further 4 hr at 20°. A crystalline precipitate was obtained, washed with water, and evaporated in vacuum to
Characterisation of synthetic triazepinone
As a standard for mass spectrometry analysis, a synthetic metformin–methylglyoxal adduct was chemically prepared and characterised. This product had the following characteristics: melting point 264–266°, elemental analysis (calculated/found): C 45.94/45.89%, H 7.29/7.15%, N 38.03/38.22%, O 8.65/8.73%. Mass spectrum showed a molecular mass of 183 compatible with the calculated molecular mass of 183.21 for C7H13N5O. The infrared spectra of this compound exhibited the absorptions assignable to C =
Discussion
Metformin is an oral antihyperglycemic agent used for the management of non-insulin-dependent diabetes mellitus (NIDDM). It is structurally related to guanidines, which elicit a marked interest in glycation studies and in the prevention of diabetic complications. The most studied guanidine compound with a clear inhibitory effect on AGE formation is aminoguanidine [14]. Several groups have shown that this compound was quite effective in inhibiting the formation of AGEs in vitro and in vivo[2].
Acknowledgements
We thank Dr. N. Chanon and Dr. T. Passemard for their collaboration with chemical analysis of the synthetic triazepinone as well as Patricia Lévêque for her technical assistance. We also thank Dr E. Michoud and Dr. E. Véricel for helpful discussions.
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