Chemical synthesis, inhibitory activity and molecular mechanism of 1-deoxynojirimycin–chrysin as a potent α-glucosidase inhibitor. Issue 61 (1st December 2021)

• Record Type: Journal Article
• Authors: Zhang, Ran; Zhang, Yueyue; Huang, Gaiqun; Xin, Xiangdong; Tang, Liumei; Li, Hao; Lee, Kwang Sik; Jin, Byung Rae; Gui, Zhongzheng
• Is Part Of: RSC advances. Volume 11:Issue 61(2021)
• Page Start: 38703
• Page End: 38711
• Publication Date: 2021-12-01
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1ra07753h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Hyperglycemia can be efficaciously regulated by inhibiting α-glucosidase activity and this is regarded as an effective strategy to treat type 2 diabetes. 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.