Synthesis, biological activity and molecular docking research of N-{(4-oxo-thiochroman-3-yl)phenyl-methyl}acetamide derivatives as α-glucosidase inhibitors.
- Author:
Guan ZHOU
;
Guo-chao LIANG
;
Xiao-yan HAN
;
Yi-fan ZHONG
;
Yun-fang DONG
;
Xiao-cong LUO
;
Hong-wei JIN
;
Ya-li SONG
- Publication Type:Journal Article
- MeSH:
Acetamides;
Glycoside Hydrolase Inhibitors;
chemical synthesis;
pharmacology;
Hypoglycemic Agents;
chemical synthesis;
pharmacology;
Molecular Docking Simulation;
Structure-Activity Relationship;
alpha-Glucosidases;
metabolism
- From:
Acta Pharmaceutica Sinica
2016;51(1):93-99
- CountryChina
- Language:Chinese
-
Abstract:
In order to develop potent antidiabetic agents that have inhibitory effect to a-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-41 were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol x L(-1). The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.
