Synthesis, in vitro inhibitory activity, kinetic study and molecular docking of novel N-alkyl–deoxynojirimycin derivatives as potential α-glucosidase inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry

卷:35

En Yuan¹  Da-Yong Peng²  Xu-Liang Nie²  Jia-Cheng Zeng³  Ji-Guang Chen³  Zhong-Ping Yin³  Ping Lin³  Xiao-Qiang Wang⁴ 

[1] College of Pharmacy, Jiangxi University of Traditional Chinese Medicine;

[2] College of Science, Jiangxi Agricultural University;

[3] Jiangxi Key Laboratory of Natural Products and Functional Foods, Jiangxi Agricultural University;

[4] State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University;

关键词: 1-deoxynojirimycin derivatives;    α-glucosidase;    inhibitor;    structure–activity relationship;    docking study;   

DOI  :  10.1080/14756366.2020.1826941

来源: DOAJ

【 摘 要 】

A series of novel N-alkyl-1-deoxynojirimycin derivatives 25 ∼ 44 were synthesised and evaluated for their in vitro α-glucosidase inhibitory activity to develop α-glucosidase inhibitors with high activity. All twenty compounds exhibited α-glucosidase inhibitory activity with IC50 values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC50 = 822.0 ± 1.5 µM). The most active compound 43 was ∼27-fold more active than acarbose. Kinetic study revealed that compounds 43, 40, and 34 were all competitive inhibitors on α-glucosidase with Ki of 10 µM, 52 µM, and 150 µM, respectively. Molecular docking demonstrated that the high active inhibitors interacted with α-glucosidase by four types of interactions, including hydrogen bonds, π–π stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the π–π stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.

【 授权许可】

Unknown