Transcript スライド 1 - 北海道大学

Effect of glycoside bond on insulin mimetic activity of flavonoid-neohesperidose conjugate
〇Ryogo Hishiki, Eisuke Kato, Jun Kawabata
Laboratory of Food Biochemistry, Research Faculty of Agriculture, Hokkaido University
Experiment 1
Introduction
Kaempferol 3-O-neohesperidoside (1), which is one of flavonoid glycosides, was reported to induce
glucose uptake in skeletal muscle cells. This compound is expected to become a new drug for Diabetes
mellitus because it shows insulin mimetic activity in nanomolar scale and probably has a mechanism
which is different from traditional model.
We recently reported that neohesperidose, which is the glycoside part of 1, is the key structure for the
activity. However, further study indicated that naringin did not show the activity in spite of containing
neohesperidose in its strucure.
Insulin Mimetic Activity of 2 & 3
Conclusion & Discussion
Objective
Based on the above result, we made two hypotheses about the mechanism. Hypothesis Ⅰ is that the
activity of 1 is induced from the released neohesperidose, because the position of the glycoside bond of 1
has the highest reactivity (blue arrow in the figure below). And hypothesis Ⅱ is that the difference of the
steric structures affects the activity (red arrow).
To investigate these possibilities, we planned two experiments. (Experiment1 & 2).
Flavonoid glycoside 2 and 3 did not show any insulin mimetic activity. This
result further supported hypothesis Ⅰ, but there was still another
possibility that altered steric hindrance was the reason of altered activity.
Then we focused on S-glycosyl bond which is more stable than O-glycosyl
one and we are currently synthesizing apigenin S-neohesperidoside (4) to
investigate the effect of steric hindrance.
Synthesis of 2 & 3
Exp.1 Seeing the activity of the flavonoid glycosides 2 and 3 whose glycosylation
positions are different from 1
Exp.2 Seeing the effect of steric hindrance by the activity of flavonoid thioglycoside 4
Assay Procedure
Experiment 2
Synthesis of 4