Accepted_test

Dual ligands of  peroxisome proliferator-activated receptors (PPAR) α and γ, called glitazars, are promising potential drugs for type 2 diabetes mellitus treatment that combine the hypolipidemic and hypoglycemic properties of  PPAR α and γ agonists in one molecule yet they have different side effects, dependent on the structural fragment, connected to the conservative part of their molecule. The aim of this study was to evaluate the hypoglycemic and hypolipidemic activity of five new potential glitazars with a dihydrobetilonic acid fragment, separated from the conservative part by linkers of different length (from 2 up to 6 carbon atoms). In this study C57BL/6 A^y/a mice on a high-calorie diet were injected for 28 days with the test compounds at a dose of 30 mg/kg. Metformin (250 mg/kg) and tesaglitasar (30 mg/kg) were used as reference drugs. On the 15^th and 30^th day of the experiment, oral glucose tolerance tests (OGTT) were carried out and the animals' weight was assessed weekl. It was found out that all of the tested compounds showed a statisticallly significant hypoglycemic effect in the OGTT. But the most pronounced action, accompanied by a substantial animals' weight loss was observed in the group of the compound with the shortest linker, consicting of 2 carbon atoms. Thus, this compound may be a basis for  the develompent of new glitazars with high efficiency and safet profile.