Evaluation of Antidiabetic and Antioxidant activity of n-Cinnamoyl Metformin Analogues

Purpose. In order to find highly active antidiabetic compounds, 8 new N-Cinnamoyl metformin analogues were synthesized. Dose selection was made on the basis of acute oral toxicity study (5 mg/kg b. wt to 2000 mg/kg b. wt) as per OECD-423 guidelines. Anti hyperglycemic activity of these 8 analogues was preliminarily evaluated by oral glucose tolerance test. Among them 2 analogues were found to be highly active. Highly active compounds were further evaluated employing alloxan model (150 mg/kg, i.p), administering drugs orally (100 mg/kg) for 7 days. On the days of 1, 3, 5 and 7 the parameters like serum glucose, triglycerides, cholesterol, High density Lipoproteins, Low density Lipoproteins, Very Low density Lipoproteins, Aspartate amino transferase and Alanine transaminase were determined. Results. The 2 analogues have shown significant glucose lowering activity. Compounds were also found to possess significant potent activity in reducing parameters like serum triglycerides, cholesterol, High density Lipoproteins, Low density Lipoproteins, Very Low density Lipoproteins, Aspartate amino transferase and Alanine Transaminase levels. These compounds were also evaluated for in vivo antioxidant properties like catalase, lipid peroxidase and reduced glutathione. Compounds displayed significant in vivo free radical scavenging activity. Conclusion. The results revealed that metformin analogues effectively lowered blood glucose, serum lipid levels and decreased oxidative stress. On the basis of our above findings, it is hoped that the study will aid in the development of new treatment for diabetes.