当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design and synthesis of novel xanthone-triazole derivatives as potential antidiabetic agents: α-Glucosidase inhibition and glucose uptake promotion.

Design and synthesis of novel xanthone-triazole derivatives as potential antidiabetic agents: α-Glucosidase inhibition and glucose uptake promotion.

Abstract：

:Inhibiting the decomposition of carbohydrates into glucose or promoting glucose conversion is considered to be an effective treatment for type 2 diabetes. Herein, a series of novel xanthone-triazole derivatives were designed, synthesized, and their α-glucosidase inhibitory activities and glucose uptake in HepG2 cells were investigated. Most of the compounds showed better inhibitory activities than the parental compound a (1,3-dihydroxyxanthone, IC50 = 160.8 μM) and 1-deoxynojirimycin (positive control, IC50 = 59.5 μM) towards α-glucosidase. Compound 5e was the most potent inhibitor, with IC50 value of 2.06 μM. The kinetics of enzyme inhibition showed that compounds 5e, 5g, 5h, 6c, 6d, 6g and 6h were noncompetitive inhibitors, and molecular docking results were consistent with the noncompetitive property that these compounds bind to allosteric sites away from the active site (Asp214, Glu276 and Asp349). On the other hand, the glucose uptake assays exhibited that compounds 5e, 6a, 6c and 7g displayed high activities in promoting the glucose uptake. The cytotoxicity assays showed that most compounds were low-toxic to human normal hepatocyte cell line (LO2). These novel xanthone triazole derivatives exhibited dual therapeutic effects of α-glucosidase inhibition and glucose uptake promotion, thus they could be use as antidiabetic agents for developing novel drugs against type 2 diabetes.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Ye GJ,Lan T,Huang ZX,Cheng XN,Cai CY,Ding SM,Xie ML,Wang B

doi

10.1016/j.ejmech.2019.05.045

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

362-373

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(19)30455-6

journal_volume

177

pub_type

杂志文章

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