Substituted guanidine compounds as inhibitors of nonenzymatic glycation invitro

Pathologic effects of the process of nonenzymatic glycation are reflected i n degenerative changes during ageing, chronic complications of diabetes mel litus and renal failure, and have also been recognised in some neurologic d iseases, such as Alzheimer's disease. Aminoguanidine has been extensively s tudied as an inhibitor of nonenzymatic glycation, both in vitro and in vivo . We investigated the inhibiting potency of substituted guanidines in the p rocess of glycation. For this purpose, a-methylguanidine-acetic acid (creat ine) and dimethylbiguanide (Metformin) were chosen. A common feature of the se compounds is the presence of guanidine group in the molecule. Creatine i s a specific muscle tissue metabolite, a nontoxic biogenic substance. Dimet hylbiguanide is a substituted molecule of guanidine structure. In clinical practice, it is used in the treatment of non-insulin dependent type of diab etes mellitus. Both agents, a-methylguanidine-acetic acid and dimethylbigua nide, tested at concentrations of 2.5, 5, 10 and 20 mmol L-1, showed a conc entration dependent inhibition of the glucose induced albumin glycation in vitro. The inhibiting effect of substituted guanidines was somewhat inferio r (17%) to the effect of aminoguanidine inhibition (52%); however, the form er substances are valuable for being safe for human use.