Nineteen New Flavanol-Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from .

The dried fruits of were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which , , , , and exhibited obvious activity against α-glucosidase with IC values of 5.2-9.0 μM, 20-35 times stronger than that of acarbose (IC, 180.0 μM); meanwhile, , -, and were PTP1B/TCPTP-selective inhibitors with IC values of 56.4-80.4 μM, 2-4 times stronger than that of suramin sodium (IC, 200.5 μM). Enzyme kinetics study indicated that compounds , , , and were α-glucosidase and PTP1B mixed-type inhibitors with values of 13.0, 11.7, 2.9, and 5.3 μM and 142.3, 88.9, 39.2, and 40.8 μM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.