Synthesis of γ ‐Butyrolactone Derivatives from Dihydrotagetone and Evaluation of Their Antidiabetic Activity

Abstract γ ‐Butyrolactone (GBL) is a five‐membered heterocycle with an ester group that received much attention in drug development. They exhibit a broad range of biological activities like antiglaucoma, antibiotics, neuroprotective, antifungal, and diuretics, along with a few antidiabetic activities. Here, six GBL derivatives were synthesized via semi‐synthetic modification of naturally occurring acyclic monoterpene dihydrotagetone (DHT) isolated from the essential oil of Tagetes minuta . All GBL derivatives were screened for α ‐glucosidase inhibitory (AGI) activity. Present studies demonstrated that ethyl substituted GBL derivative i. e ., 5‐ethyl‐5‐isobutyl‐3‐methyldihydrofuran‐2(3 H )‐one (IC 50 =5.88±0.21 μM) has the nearly similar α ‐glucosidase inhibitory activity to the reference drug acarbose (IC 50 = 5.47±0.62 μM) while the DHT (IC 50 =15.32±1.44 μM) and its acid version i. e ., 2,6‐dimethyl‐4‐oxoheptanoic acid (IC 50 =18.61±0.87 μM) has lowest inhibition activity in the same assay. Furthermore, molecular docking studies were conducted to explore binding interactions of the GBL derivatives with α ‐glucosidase. This study discovered a new class of α ‐glucosidase inhibitors.