Thiazolidinedione-Pyrimidine Hybrid as Potential Antidiabetic Agents and Their Cardioprotective Effect

The leading cause of death in diabetic patients is diabetic cardiomyopathy (DCM). Despite the availability of anti-diabetic medications which effectively curb the hyperglycemia, the drug molecule which alleviates the severity of DCM along with the maintenance of a normoglycemic profile of diabetic patients is still unexplored. In this study, a series of thiazolidinedione-pyrimidine hybrid compounds were synthesized, and their anti-diabetic potential was explored in STZ-NA induced diabetic Wistar rats. The role of these compounds in DCM was also evaluated. The most potent compound, PT-5, showed significant reduction in blood glucose levels (from 129 to 115 mg/dL in 2 h) in comparison to the standard drug Pioglitazone (135–117 in 2 h). The biochemical estimations of AST, ALT, ALP, Troponin T, Cκ-MB, CRP, and LDH levels illustrated that the levels appreciably came back to normal in the PT-1, PT-5, and PT-13 treatment groups. The cardioprotective role was further validated by cardiac tropism indices and levels of antioxidants in cardiac tissue. The biochemical assessments were further validated through histopathological studies. This research indicates that these derivatives hold promise for the development of new potential antidiabetic agents.