α-Glucosidase inhibitory flavonol glycosides from Cyclocarya paliurus (Batalin) Iljinskaja and their kinetics characteristics

Seven previously undescribed flavonol glycosides including four rare flavonol glycoside cyclodimers, dicyclopaliosides A -C ( 1 - 3 ) with truxinate type and dicyclopalioside D ( 4 ) with truxillate type, as well as three kaempferol glycoside derivatives cyclopaliosides A -C ( 5 - 7 ), were obtained from the leaves of Cyclocarya paliurus . Their structures were elucidated by extensive spectroscopic methods and chemical analyses. All compounds were evaluated for their inhibitory alpha-glucosidase activities. Among them, compounds 1 - 4 display strong inhibitory activities with IC 50 values of 82.76 +/- 1.41, 62.70 +/- 4.00, 443.35 +/- 16.48, and 6.31 +/- 0.88 nM, respectively, while compounds 5 - 7 showed moderate activities with IC 50 values of 4.91 +/- 0.75, 3.64 +/- 0.68, and 5.32 +/- 0.53 mu & Mcy;, respectively. The structure -activity relationship analysis assumed that the cyclobutane cores likely contribute to the enhancement of alpha-glucosidase inhibitory activities of dimers. Also, the interaction mechanism between flavonol glycoside dimers and alpha-glucosidase were explored by the enzyme kinetic assay, indicating that compounds 1 - 3 exhibited mixed -type inhibition, while 4 showed uncompetitive inhibition. Additionally, the active compounds have also undergone molecular docking evaluation.