Newly emerged xanthone derivatives have attracted considerable interests as a novel class of potent α-glucosidase inhibitors. To provide insights into the inhibitory and binding mechanisms of xanthone-based inhibitors toward α-glucosidase, we carried out experimental and theoretical studies on two typical xanthone derivatives, i.e., 1,3,7-trihydroxyxanthone and 1,3-dihydroxybenzoxanthone. The results indicate that these two xanthone derivatives belong to noncompetitive inhibitors and induce a loss in the α-helix content of the secondary structure of α-glucosidase. Docking simulation revealed the existence of multiple binding modes, in which polyhydroxyl groups and expanded aromatic rings acted as two key pharmacophores to form H-bonding and π-π stacking interactions with α-glucosidase. The fact that 1,3,7-tridroxyxanthone and 1,3-dihydroxybenzoxanthone exhibited significant synergetic inhibition to α-glucosidase strongly suggests that both xanthone derivatives simultaneously bind to the distinct noncompetitive sites of yeast's α-glucosidase. On the basis of the plausible binding clues, synergetic inhibition can be developed to be a promising strategy to achieve enhanced inhibitory activities.

• PMID: 24083955
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Liu Y, Ma L, Chen WH, Park H, Ke Z, Wang B

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