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

ABSTRACT: Hyperglycemia can be efficaciously regulated by inhibiting α-glucosidase activity and this is regarded as an effective strategy to treat type 2 diabetes. 1-Deoxynojimycin, an α-glucosidase inhibitor, can penetrate cells rapidly to potently inhibit α-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 α-glucosidase catalytic site, thereby exhibiting excellent α-glucosidase inhibitory activity (IC₅₀ = 0.51 ± 0.02 μM). Kinetics analyses revealed that compound 6 inhibited the activity of α-glucosidase in a reversible and mixed competitive manner. Fluorescence quenching and UV-Vis spectra showed that compound 6 changed the conformation of the α-glucosidase via complex formation, which triggered a static fluorescence quenching of the enzyme protein.

SUBMITTER: Zhang R

PROVIDER: S-EPMC9044198 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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

Zhang Ran R Zhang Yueyue Y Huang Gaiqun G Xin Xiangdong X Tang Liumei L Li Hao H Lee Kwang Sik KS Jin Byung Rae BR Gui Zhongzheng Z

RSC advances 20211101 61

Hyperglycemia can be efficaciously regulated by inhibiting α-glucosidase activity and this is regarded as an effective strategy to treat type 2 diabetes. 1-Deoxynojimycin, an α-glucosidase inhibitor, can penetrate cells rapidly to potently inhibit α-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 a ...[more]

PMID: 35493254

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Dataset Information

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

Publications

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

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