1. Synthesis, in vitro inhibitory activity, kinetic study and molecular docking of novel N-alkyl–deoxynojirimycin derivatives as potential α-glucosidase inhibitors
- Author
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Zhong-Ping Yin, Xu-Liang Nie, Ji-Guang Chen, Xiaoqiang Wang, Da-Yong Peng, Jia-Cheng Zeng, En Yuan, and Ping Lin
- Subjects
1-Deoxynojirimycin derivatives ,structure–activity relationship ,1-Deoxynojirimycin ,Stereochemistry ,RM1-950 ,Inhibitory postsynaptic potential ,Benzylidene Compounds ,01 natural sciences ,Structure-Activity Relationship ,Drug Discovery ,Humans ,Structure–activity relationship ,Glycoside Hydrolase Inhibitors ,Alkyl ,Pharmacology ,chemistry.chemical_classification ,Glucosamine ,010405 organic chemistry ,α glucosidase ,Hydrogen Bonding ,alpha-Glucosidases ,General Medicine ,In vitro ,0104 chemical sciences ,inhibitor ,Molecular Docking Simulation ,Kinetics ,010404 medicinal & biomolecular chemistry ,chemistry ,α-glucosidase ,Therapeutics. Pharmacology ,Acarbose ,Hydrophobic and Hydrophilic Interactions ,docking study ,Research Article ,Research Paper - Abstract
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 Kiof 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.
- Published
- 2020