Exploring the structure–activity relationship and interaction mechanism of flavonoids and α-glucosidase based on experimental analysis and molecular docking studies

作者：Hongjin Tang, Lin Huang, Chunyong Sun, Dongsheng Zhao · 发表于：Food & Function · 年份：2020 · DOI：10.1039/c9fo02806d · 被引用次数：87 · 研究领域：Natural Antidiabetic Agents Studies、Phytochemicals and Antioxidant Activities、Protein Interaction Studies and Fluorescence Analysis

α-Glucosidase (AG) has always been an indispensable drug target for the treatment of type 2 diabetes. Herein, an integrated method consisting of enzyme kinetics, multi-spectroscopy assay and molecular simulations was used to investigate the structure-activity relationship and interaction mechanism of flavonoids and AG. As a result, a small amount of flavonoids was found to present excellent inhibitory activity on AG, such as 3, 5, 6, 8, 10, 17, 19, 21, 22 and 34. Further analysis of the structure-activity relationship illustrated that hydroxylation at the positions C3, C6, C3' and C4' of flavonoids caused an increase in the inhibitory activity of AG, whereas the methoxylation at the corresponding positions would decrease the activity. Also, it was found that the glycosylation and hydrogenation of the C2[double bond, length as m-dash]C3 double bond would distinctly reduce the inhibition potency. Therefore, various groups at different positions of flavonoids exhibited an upward and downward tendency in the activity. According to the fluorescence quenching assay, all of the test flavonoids could effectively quench the intrinsic fluorescence of AG based on either the static or mixed static-dynamic mechanism. Besides, the thermodynamic parameters of the representative flavonoid 19 revealed the spontaneous characteristic of the binding process with AG, and highlighted the critical role of the hydrophobic interaction and hydrogen bonds. Moreover, the results obtained from the synchr...