Design, Synthesis, Molecular Docking and Hypoglycemic Activity of Novel Coumarin Analogues

Abstract

Diabetes and its associated conditions are significant causes of morbidity and mortality. Despite the abundance of available medications for diabetes treatment, their limitations have spurred ongoing research in this field. Consequently, there is a need to discover a potential therapeutic molecule for managing diabetes and its complications. In current research work a series of novel coumarin analogs (5a–5e) were designed, synthesized, characterized through FTIR, ¹H NMR, ¹³C NMR, and mass spectroscopy and evaluated for antidiabetic property. Molecular docking study was performed to link its binding affinity toward AMPK. DPPH scavenging assay was performed for in vitro antioxidant activity, for reference standard ascorbic acid was taken. In vivo hypoglycemic activity was performed on streptozotocin and nicotinic acid induced diabetic rats. All synthesized molecule showed good docking, score among them compound 5b has lowest docking score −11.25 kcal/mol. Molecule 5b and 5c showed greater antioxidant potential with good IC₅₀ value, i.e., 20.4 g/mL and 21.6 g/mL. In vivo antidiabetic study showed good control on blood glucose level, cholesterol, triglyceride, Hb1AC as well as SGOT and SGPT level on animals fed 5b when compared to metformin. This result showed that test molecule 5b has potential to lower the blood glucose level without causing any toxicity.