Comprehensive study on the inhibition mechanism of alpha-glucosidase by flavonoids via kinetic and structural analysis

被引:0
|
作者
Jin Young Lee
Hoe-Suk Lee
Yu-Young Lee
Mi-Hyang Kim
Hyun-Joo Kim
Narae Han
Moon Seok Kang
Young Joo Yeon
机构
[1] National Institute of Crop Science,Crop Post
[2] Rural Development Administration,harvest Technology & Research Division, Department of Central Area Crop Science
[3] Gangneung-Wonju National University,Department of Biochemical Engineering
来源
Biotechnology and Bioprocess Engineering | 2024年 / 29卷
关键词
Alpha-glucosidase; Flavonoid; Enzyme inhibition mode; Structure–activity relationship; Enzyme–ligand docking;
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摘要
Flavonoid consists of an extensive range of compounds with variable inhibitory activities against alpha-glucosidase, implicating its role in the prevention and treatment of diabetes caused by uncontrolled increases in the blood glucose level. Comprehensive study on a selected assortment of flavonoids for their degrees of inhibition, types of inhibitory mode and the structure–function relationship both in terms of the ligand chemical structure and in the context of the enzyme–inhibitor binding complex is therefore necessary to predict and develop efficient flavonoid inhibitors. Herein, flavonoids based on flavone, flavonol, flavanone and isoflavone skeletons in their aglycone and glycone forms were analyzed to this purpose. Most aglycones showed excellent inhibition, while glycones showed relatively low activities. Competitive, noncompetitive and mixed inhibition modes were observed from different types of flavonoids, and their molecular mechanisms by binding to the active or allosteric sites of alpha-glucosidase were analyzed via the docking study. Quercetin with a superior competitive inhibitory activity bound near the catalytic residues within the active site, whereas other glycosylated quercetin derivatives bound at more distal sites. Mixed inhibitors resulted in opposite binding conformations in the allosteric site depending on whether they show more competitive-like or uncompetitive-like behaviors, while the noncompetitive inhibitor could bind in both conformations.
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页码:413 / 425
页数:12
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