Indole alkaloids from Uncaria rhynchophylla and their inhibitory activities against α-glucosidase

Sixteen indole alkaloids were isolated from the hook-bearing stems of Uncaria rhynchophylla (Rubiaceae family), including seven undescribed ones, uncarialines F-L (1-5, 7, and 8), and a naturally occurring alkaloid, 3-epicorynanthine (6). Among them, alkaloids 1 and 2 were identified as rare quaternary ammonium alkaloids, and alkaloid 7 exhibited an unprecedented indole alkaloid framework. Their structures were characterized by a comprehensive analysis of NMR, MS, ECD and single-crystal X-ray diffraction. Notably, alkaloid 5 demonstrate potent inhibitory activity against α-glucosidase, with an IC₅₀ value of 18.45 ± 0.77 μM. Furthermore, the inhibitory kinetics of α-glucosidase revealed that alkaloid 5 belong to the mix inhibition type. Molecular docking analysis showed that alkaloid 5 possessed superior binding affinity with α-glucosidase (-10.7 kcal/mol).