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

摘要

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(3H)-one (IC_(50) = 5.88±0.21 μM) has the nearly similar a-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.