Synthesis and Biological Evaluation of Some Novel PPAR-γ agonists for the Management of Type II Diabetes

Abstract

Diabetes mellitus (DM) is a progressive disease characterized by hyperglycemia due to insulin deficiency and insulin resistance or both. The fasting and postprandial blood glucose gets elevated, exposing the patient to acute and chronic complications (micro- and macro-vascular) leads to blindness, kidney failure, heart disease, stroke and amputations. Diabetes mellitus is one of the most common endocrine disorders affecting almost 6% of the world's population. The number of diabetic patients will reach 300 million in 2025. More than 97% of these patients will have type II diabetes. "Glitazones," bind to ppar-γ, a type of nuclear regulatory proteins involved in transcription of genes regulating glucose and fat metabolism. These PPAR-γ acts on Peroxisome Proliferator Responsive Elements (PPRE). In the present article, Rhodanine analogs were screened for their anti diabetic activity. Rosiglitazone is used as a reference standard. The compounds R2, R5 and R7 shows better activity than the reference compound and was found to be effective as compared to the other synthesized compounds. The determined fasting blood glucose levels were monitored and the decrease in the blood glucose level was calculated. Some of the synthesized Rhodanine derivatives have shown considerable improved efficacy and improved biological response which is enough reason to believe that PPARγ is a promising target for the management of type II diabetes and that Rhodanine analogs have it in them to illicit a biological response out of the receptor.