Diarylheptanoid-chalcone hybrids with PTP1B and α-glucosidase dual inhibition from Alpinia katsumadai

Abstract

The EtOH extracts of the dried seeds of Alpinia katsumadai were revealed with hypoglycemic effects on db/db mice at the concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 16 new diarylheptanoid-chalcone hybrids, katsumadainols A1−A16 (1–16), together with 13 known analogues (17–29), were isolated from A. katsumadai under the guidance of bioassay. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which compounds 1–3, 5–7, 11–14, 21–25, and 27 showed PTP1B/TCPTP selective inhibition with IC50 values ranging from 22.0 to 96.7 μM, which were 2–10 times more active than sodium orthovanadate (IC50, 215.7 μM). All compounds exhibited obvious inhibition against α-glucosidase with IC50 values of 2.9–29.5 μM, indicating 6–59 times more active than acarbose (IC50, 170.9 μM). Study of enzyme kinetics indicated compounds 1, 3, and 12 were PTP1B and α-glucosidase mixed-type inhibitors with Ki values of 13.1, 12.9, 21.6 μM, and 4.9, 7.4, 3.4 μM, respectively.