Synthesis, biological activity and molecular docking research of N-{(4-oxo-thiochroman-3-yl)phenyl-methyl}acetamide derivatives as α-glucosidase inhibitors
10.16438/j.0513-4870.2015-0687
- VernacularTitle:N-{[(硫色满-4-酮-3-基)-苯基]-甲基}乙酰胺类化合物的合成、α-葡萄糖苷酶抑制活性评价及分子对接研究
- Author:
Guan ZHOU
1
;
Guo-chao LIANG
1
;
Xiao-yan HAN
1
;
Yi-fan ZHONG
1
;
Yun-fang DONG
2
;
Xiao-cong LUO
1
;
Hong-wei JIN
3
;
Ya-li SONG
1
Author Information
1. College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, China
2. Yung Shin Pharm. Ind. (Kunshan) Co., Ltd., Suzhou 215300, China
3. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
thiochromanone;
α-glucosidase inhibitor;
one-pot synthesis;
β-acetamido ketone
- From:
Acta Pharmaceutica Sinica
2016;51(1):93-
- CountryChina
- Language:Chinese
-
Abstract:
In order to develop potent antidiabetic agents that have inhibitory effect to α-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-4l 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·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.
