Chemical synthesis, inhibitory activity and molecular mechanism of 1-deoxynojirimycin-chrysin as a potent alpha-glucosidase inhibitor

文献类型： 外文期刊

第一作者： Zhang, Ran

作者： Zhang, Ran;Zhang, Yueyue;Huang, Gaiqun;Xin, Xiangdong;Tang, Liumei;Li, Hao;Gui, Zhongzheng;Zhang, Ran;Li, Hao;Gui, Zhongzheng;Huang, Gaiqun;Lee, Kwang Sik;Jin, Byung Rae

作者机构：

期刊名称：RSC ADVANCES （ 影响因子：3.361； 五年影响因子：3.39 ）

ISSN：

年卷期： 2021 年 11 卷 61 期

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收录情况： SCI

摘要： Hyperglycemia can be efficaciously regulated by inhibiting alpha-glucosidase activity and this is regarded as an effective strategy to treat type 2 diabetes. 1-Deoxynojimycin, an alpha-glucosidase inhibitor, can penetrate cells rapidly to potently inhibit alpha-glucosidase in a competitive manner. However, the application of 1-deoxynojimycin is limited by its poor lipophilicity and low bioavailability. Herein, three 1-deoxynojimycin derivatives 4-6 were designed and synthesized by linking 1-deoxynojimycin and chrysin to ameliorate the limitations of 1-deoxynojimycin. Among them, compound 6, a conjugate of 1-deoxynojimycin and chrysin linked by an undecane chain, could better bind to the alpha-glucosidase catalytic site, thereby exhibiting excellent alpha-glucosidase inhibitory activity (IC50 = 0.51 +/- 0.02 mu M). Kinetics analyses revealed that compound 6 inhibited the activity of alpha-glucosidase in a reversible and mixed competitive manner. Fluorescence quenching and UV-Vis spectra showed that compound 6 changed the conformation of the alpha-glucosidase via complex formation, which triggered a static fluorescence quenching of the enzyme protein.

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