Design, synthesis, biological evaluation, and docking study of new triazole-phenylacetamide derivatives as α-glucosidase inhibitors

被引：20
作者：
Luo, Shuang [1 ,3 ]
Yang, Wei [1 ,3 ]
Huang, Yong [4 ]
Peng, Zhiyun [2 ]
Wang, Guangcheng [1 ]
机构：
[1] Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guizhou Prov Key Lab Pharmaceut, Guiyang, Peoples R China
[2] Guizhou Med Univ, Affiliated Hosp, Clin Trails Ctr, Guiyang, Peoples R China
[3] Guizhou Med Univ, Sch Pharm, Guiyang, Peoples R China
[4] Guizhou Med Univ, Engn Res Ctr Dev & Applicat Ethn Med & TCM, Minist Educ, Guiyang, Peoples R China
来源：
BIOORGANIC CHEMISTRY | 2023年 / 141卷
关键词：
T2DM; alpha-Glucosidase inhibitor; Triazole; Phenylacetamide; MOLECULAR DOCKING; FLAVONOIDS; EFFICIENT; AMYLASE;
D O I：
10.1016/j.bioorg.2023.106844
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
To discover potent alpha-glucosidase inhibitors, a class of novel triazole-phenylacetamide derivatives (5a-5p) were designed, prepared, and tested for their alpha-glucosidase inhibitory effects. All tested compounds (5a-5p) displayed a strong alpha-glucosidase inhibitory activity (IC50 = 6.69 +/- 0.18-113.65 +/- 2.94 mu M) in comparison with the positive control acarbose (IC50 = 723.06 +/- 11.26 mu M). Thereinto, 5g (IC50 = 6.69 +/- 0.18 mu M) showed the best anti-alpha-glucosidase activity and behaved as a mixed-type inhibitor with the value of K-i and K-is to be 1.65 mu M and 4.54 mu M, respectively. Besides, fluorescence quenching experiment, three-dimensional fluorescence spectra assay, circular dichroism analysis, and molecular docking studies indicated that 5g may inhibit alpha-glucosidase activity by binding with its active site as well as changing the secondary structure of alpha-glucosidase. Combined with the inhibition effect on the rise of postprandial blood glucose level and low cytotoxicity of 5g, it could be concluded that these title compounds may play a role as lead compounds to develop novel alpha-glucosidase inhibitors.
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页数：11
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