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

摘要

gamma-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 rt-glucosidase inhibitory (AGI) activity. Present studies demonstrated that ethyl substituted GBL derivative i.e, 5-ethyl-5-isobutyl-3-methyldihydrofuran2(3H)-one (IC50 =5.88 +/- 0.21 mu M) has the nearly similar alpha-glucosidase inhibitory activity to the reference drug acarbose (IC50 = 5.47 +/- 0.62 mu M) while the DHT (IC50 = 15.32 +/- 1.44 mu M) and its acid version i.a, 2,6-dimethyl-4-oxoheptanoic acid (IC50 = 18.61 +/- 0.87 mu M) has lowest inhibition activity in the same assay. Furthermore, molecular docking studies were conducted to explore binding interactions of the GBL derivatives with alpha-glucosidase. This study discovered a new class of alpha-glucosiciase inhibitors.