Synthesis of Novel Acetylinc Derivative of Metformin as a DPP-4 Inhibitors and Study its Effects on Sera of Rabbits with induced Diabetes

Abstract

The study aimed to prepare novel derivative of metformin similar to the work of the enzyme inhibitors DPP-4 and so the need for new inhibitors may be a side effect with less addition to linking types of drugs have a stronger effect on patients with diabetes and to study the impact of this derivative inside the living cell has been prepared derived through interaction metformin with propargyl chloride. It was to make sure the chemical structure by using analytical and spectral methods (FT-IR, ¹H-NMR, and ¹³C-NMR), and the results confirming the obtained structures,  then purified by column chromatography by using silica gel as stationary phase and methanol as a mobile phase. The study is derived on the impact of rabbits where they were taking the 40 rabbits with similar weights and were divided into four groups (10 rabbits per group) weredivided as follows, the first group G1 obtained as a control group, which did not gave any things. The second group G2 has injected by aloxane a concentration of 120 mg / kg using syringes medical capacity of 3 ml to inject rabbits in the vein ear and after two hours of injection they were given glucose solution of 10%, the confirmed they injured rabbits diabetes by measuring blood sugar to 10 rabbits have been selected randomly and then it was taken two sets of this group, the third group G3 were given a drug sitagliptin with concentration of 10 mg / kg, and the fourth group G4, were given the prepared derivative with concentration of 8 mg / kg for 3 days and pulled blood samples after the last dose on the third day. Serum used in determination of lipid profile,DPP-4 activity,alanine transaminase(ALT),Aspartate transaminase(AST) and insulin. Results of statistical analysis showed a significant decrease in the level of FBG and  DPP-4 activity  of  the prepared derivative, and also showed a decrease in the level of cholesterol, triglyceride, LDL and VLDL, while  results showed increase in HDL level in G4 comparing to G1.

Keywords : Diabetes Mellitus , Dipeptidylpeptidase -4  , metformin .