Inhibition of α-glucosidase and α-amylase decreases postprandial blood glucose levels and delays glucose absorption, making it a treatment strategy for type 2 diabetes. This study examined in vivo and in vitro antidiabetic activities of natural prenylchalconaringenins 1 and 2 and prenylnaringenins 3 and 4, found in hops and beer. 3′-Geranylchalconaringenin (2) competitively and irreversibly inhibited α-glucosidase (IC50 = 1.08 μM) with activity 50-fold higher than that of acarbose (IC50 = 51.30 μM) and showed moderate inhibitory activity against α-amylase (IC50 = 20.46 μM). Docking analysis substantiated these findings. In addition, compound 2 suppressed the increase in postprandial blood glucose levels and serum levels of total cholesterol and triglycerides in streptozotocin-induced diabetic mice. Taken together, these results suggest that 2 has dual inhibitory activity against α-glucosidase and α-amylase and alleviates diabetic hyperglycemia and hyperlipidemia, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.Keywords: diabetes; docking; prenylchalconaringenin; prenylnaringenin; α-amylase; α-glucosidase;

A series of novel tetracyclic oxindole derivatives were synthesized via tandem Suzuki coupling–Michael addition reaction catalyzed by palladium. Twenty derivatives were designed and synthesized in 6–8 steps in 8–20% overall yields. Their structures were confirmed by 1H, 13C NMR and LC/MS. These compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compounds 7c, 7d, 7e, 7g, 7h, and 7i exhibited IC50 values of 32.3, 12.1, 15.7, 29.0, 16.0, and 4.8 μM, respectively, with potency all higher than that of the control standard acarbose (IC50 = 115.8 μM). Molecular docking studies revealed the existence of potential hydrogen bonding and hydrophobic interaction between the enzyme and the active compound 7i.