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

• Published in: Chinese journal of chemistry Vol. 39; no. 11; pp. 3051 - 3063
• Main Authors: He, Xiao‐Feng, Chen, Ji‐Jun, Li, Tian‐Ze, Hu, Jing, Huang, Xiao‐Yan, Zhang, Xue‐Mei, Guo, Yuan‐Qiang, Geng, Chang‐An
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH & Co. KGaA 01.11.2021; Wiley; Wiley Subscription Services, Inc
• Subjects: Acarbose; Alpinia; Alpinia katsumadai; Biological activity; Chemistry; Chemistry, Multidisciplinary; Diabetes mellitus; Glucosidase; Glycogen; Glycogen phosphorylase; Glycogens; Hybrids; Katsumadainols B1—B15; Natural products; Phosphorylase; Physical Sciences; Science & Technology; Seeds; Structure elucidation; CONSTITUENT; GLYCOGEN-PHOSPHORYLASE; ALPHA-GLUCOSIDASE; Alpinia katsumadai; Katsumadainols B-1-B-15; Biological activity; SEEDS; DUAL INHIBITION; ABSOLUTE-CONFIGURATION; Natural products; TYROSINE-PHOSPHATASE 1B; CHALCONE; Structure elucidation; DERIVATIVES
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.202100469

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 B1—B15 (1—15), together with eight known ones (16—23). Compounds 4—10 and 12—21 exhibited activity against GPa with IC50 values of 10.1—95.4 μmol/L; compounds 4, 5, 16, and 17 displayed inhibitory effects on α‐glucosidase with IC50 values of 7.1, 12.4, 7.2, and 8.3 μmol/L, obviously higher than acarbose (IC50, 209.1 μmol/L); compounds 4—6, 14, 16—20, 22, and 23 were PTP1B/TCPTP selective inhibitors with IC50 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. Fifteen new diarylheptanoid‐flavanone hybrids, katsumadainols B1—B15 (1—15), along with eight known ones (16—23), were isolated from the seeds of Alpinia katsumadai. Compounds 4, 5, 16, and 17 represented a promising class of multiple‐target antidiabetic agents inhibiting GPa, α‐glucosidase, PTP1B, and DPP4.