Kalapko-Matsievska O. The experimental investigation of N,N/-(ethane-1,2-dyyil)bis(quinoline-2-carboxamide) as a potential hypoglycemic agent

The thesis is devoted to the experimental study of N,N'-(ethane-1,2-dyyil)bis(quinoline-2-carboxamide) (N,N'-EBQC) in the treatment of diabetes mellitus (DM) and insulin resistance (IR). N,N'-EBQC at the (i/p) administration belongs to the moderately toxic substances, and at the i/g administration belongs to the low-toxic substances .The effect of N,N'-EBQC was investigated in comparison with the diacamph hydrochloride (DH) and metformin. On the model of the alloxane DM N,N'-EBQC has an antihyperglycemic effect with i/p administration at a dose of 1.5 mg/kg, with i/g administration - in the dose range of 7.92-31.67 mg/kg (ED50 is 11,64 mg/kg,the therapeutic index - 54,42). For normoglycemics, N,N'-EBQC is not presented in the hypoglycemic action. On the model of the alioxane DM N,N'-EBQC eliminates the activation of the POL, improves the state of carbohydrate metabolism, increases the lowered insulin content in the blood and normalizes the level of the pro-inflammatory marker TNF-α; as comparators, reduces destruction and increases the proliferation of insulinocytes, improves histostructure of the liver for 3 days. On the sucrose model, N,N'-EBQC reduces the severity of IR and improves the glucose tolerance. The mechanism of antihyperglycemic action of N,N'-EBQC involves stimulation of imidazoline receptors of types I1 and I2. The involvement of stimulation of the I2- but not the I1-imidazoline receptors in the mechanism of the antihyperglycemic action of DH and metformin has been proved. The results experimentally substantiate the feasibility of the creation of the original antidiabetic drug on the basis of N,N'-EBQC.