Diarylheptanoid‐flavanone Hybrids as Multiple‐target Antidiabetic Agents from Alpinia katsumadai

Main observation and conclusion The EtOAc fraction of Alpinia katsumadai seeds showed significant inhibition on glycogen phosphorylase a (GPa) with inhibitory ratios of 97.9% and 64.6% at concentrations of 200 and 100 μg/mL, respectively. Bioactivity‐guided isolation afforded 15 new diarylheptanoid‐flavanone hybrids, katsumadainols B 1 —B 15 (1—15), together with eight known ones (16—23). Compounds 4—10 and 12—21 exhibited activity against GPa with IC 50 values of 10.1—95.4 μmol/L; compounds 4, 5, 16, and 17 displayed inhibitory effects on α ‐glucosidase with IC 50 values of 7.1, 12.4, 7.2, and 8.3 μmol/L, obviously higher than acarbose (IC 50 , 209.1 μmol/L); compounds 4—6, 14, 16—20, 22, and 23 were PTP1B/TCPTP selective inhibitors with IC 50 values of 40.7—95.8 μmol/L; compounds 4, 5, 16, and 17 showed DPP4 inhibitory effects with inhibitory ratios of 50.0%—54.2% (200 μmol/L). Diarylheptanoid‐flavanone hybrids (4, 5, 16, and 17) with a p ‐hydroxybenzyl at C‐6 position represent a promising class of multiple‐target antidiabetic agents inhibiting GPa, α ‐glucosidase, PTP1B, and DPP4.