Coumarin analogues (5f–5j) were rationally designed and synthesized guided by molecular docking and ADME profiling. In vivo assessment in STZ+NA-induced diabetic rats demonstrated significant antidiabetic efficacy. These findings highlight the potential of the synthesized analogues as promising therapeutic leads for diabetes management.

Abstract

Coumarins are a class of compounds with a pronounced wide range of biological activities. Their biological activity and potential application are highly dependent on their structure. In present research work a series of novel coumarin analogues (5f-5j) were designed, synthesized, and characterized through different spectroscopy methods and evaluated for its hypoglycemic property. Molecular docking study was performed against α-amylase and AMPK. In vitro antioxidant activity was performed by DPPH scavenging assay, ascorbic acid was taken for reference. Compounds showed inhibitory activity against α-amylase in in vitro inhibition assay. Evaluation of hypoglycemic activity was carried out on animal model. Entire synthesized molecule showed good docking score for both the target protein, among them compound 5f and 5j showed least energy score −10.77 and −10.75 kcal/mol for α amylase, whereas for AMPK energy score was −11.00 kcal/mol and −11.80 kcal/mol respectively. Compound 5f and 5g showed highest antioxidant potential with IC₅₀ value 20.96 g/mL and 19.11 g/mL. Both the molecule 5f and 5g showed reduction in blood glucose level, maintained Hb1AC level after 4 week treatment. Slight regeneration of beta cells observed in histological study of rat's pancreas treated with compound 5f and 5g. This outcome indicated the hypoglycemic potential of 5f and 5g without causing any toxicity.