LAUSR

Abstract Guanidine derivatives are widely used antidiabetic drugs. Metformin (biguanide) is the first-line therapy for the type 2 diabetes mellitus due to its multi-target and pleiotropic effects. Compounds that comprise guanidine moiety integrated in a heterocycle, i.e. cyclic guanidines, represent an increasing area of interest. We have synthesized and studied hypoglycemic effects of a range of cyclic guanidines, namely 2-aminobenzimidazoles and structurally related imidazo[1,2-a]-, pyrimido[1,2-a]-, pyrrolo[1,2-a]-, triazolo[1,5-a]benzimidazole tricyclic derivatives. We have determined the potential of these scaffolds using molecular modeling and QSAR analysis. Experimental studies have shown that N9-(diethylamino)ethyl-2,3-dihydro-imidazo[1,2-a]benzimidazole (RU-254, diabenol) exhibits potent antidiabetic effects along with a low toxicity. We have found that diabenol exerts long-term glucose-lowering effects in prediabetic and diabetic animals, stimulates the first phase of insulin secretion and reduces the rate of liver glycogenolysis. Additionally, diabenol has been shown to exhibit antiplatelet, geroprotective and antitumor activities in animals. Clinical trials confirm that diabenol produces a range of antidiabetogenic effects such as improved glycemia, reduced HbA1c, stimulation of insulin secretion, decreased thrombogenic potential of blood and ameliorated hemorheology.