Design, synthesis and biological evaluation of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) hydrazine-1-carboxamide derivatives as α-glucosidase inhibitors

被引：17

作者：

Zhang, Jin-He ^{[1
]}

Xie, Hong-Xu ^{[1
]}

Li, Yue ^{[1
]}

Wang, Kai-Ming ^{[1
]}

Song, Zhiling ^{[2
]}

Zhu, Kong-Kai ^{[1
,2
]}

Fang, Lei ^{[1
]}

Zhang, Juan ^{[1
]}

Jiang, Cheng-Shi ^{[1
]}

机构：

[1] Univ Jinan, Sch Biol Sci & Technol, Jinan 250022, Peoples R China

[2] Qingdao Univ Sci & Technol, Coll Chem & Mol Engn, Qingdao 266042, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2021年 / 52卷

基金：

中国国家自然科学基金;

关键词：

Hydrazine-carboxamide; alpha-Glucosidase inhibitor; Molecular docking; Cytotoxicity; Hypoglycemic; IN-VITRO EVALUATION; MOLECULAR DOCKING; ISATIN DERIVATIVES; DIABETES-MELLITUS; POTENT;

D O I：

10.1016/j.bmcl.2021.128413

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this present study, a series of novel (E)-2-benzylidene-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) hydrazine-1-carboxamide derivatives against alpha-glucosidase were designed and synthesized, and their biological activities were evaluated in vitro and in vivo. Most of the designed analogues exhibited better inhibitory activity than the marketed acarbose, especially the most potent compound 7 with an IC50 value of 9.26 +/- 1.84 mu M. The direct binding of 7 and 8 with alpha-glucosidase was confirmed by fluorescence quenching experiments, and the kinetic and molecular docking studies revealed that 7 and 8 inhibited alpha-glucosidase in a non-competitive manner. Cytotoxicity bioassay indicated compounds 7 and 8 were non-toxic towards LO2 and HepG2 at 100 mu M. Furthermore, both compounds were demonstrated to have in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-treated rats.

引用

页数：5

共 37 条

[1] Fluorescent-tagged sp2-iminosugars with potent β-glucosidase inhibitory activity [J].

Aguilar-Moncayo, Matilde ;

Garcia-Moreno, M. Isabel ;

Stuetz, Arnold E. ;

Fernandez, Jose M. Garcia ;

Wrodnigg, Tanja M. ;

Mellet, Carmen Ortiz .

BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (21) :7439-7445

[2] N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3 [J].

Angell, Richard M. ;

Atkinson, Francis L. ;

Brown, Murray J. ;

Chuang, Tsu Tshen ;

Christopher, John A. ;

Cichy-Knight, Maria ;

Dunn, Allison K. ;

Hightower, Kendra E. ;

Malkakorpi, Susanna ;

Musgrave, James R. ;

Neu, Margarete ;

Rowland, Paul ;

Shea, Robyn L. ;

Smith, Jeffery L. ;

Somers, Donald O. ;

Thomas, Sonia A. ;

Thompson, Gladstone ;

Wang, Ruolan .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (05) :1296-1301

[3] Analogues of xanthones- -Chalcones and bis-chalcones as α-glucosidase inhibitors and anti-diabetes candidates [J].

Cai, Chao-Yun ;

Rao, Li ;

Rao, Yong ;

Guo, Jin-Xuan ;

Xiao, Zhi-Zun ;

Cao, Jing-Yu ;

Huang, Zhi-Shu ;

Wang, Bo .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 130 :51-59

[4] IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045 [J].

Cho, N. H. ;

Shaw, J. E. ;

Karuranga, S. ;

Huang, Y. ;

Fernandes, J. D. da Rocha ;

Ohlrogge, A. W. ;

Malanda, B. .

DIABETES RESEARCH AND CLINICAL PRACTICE, 2018, 138 :271-281

[5] Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes -: Many differences, few similarities [J].

Cnop, M ;

Welsh, N ;

Jonas, JC ;

Jörns, A ;

Lenzen, S ;

Eizirik, DL .

DIABETES, 2005, 54 :S97-S107

[6] Synthetic heterocyclic candidates as promising α-glucosidase inhibitors: An overview [J].

Dhameja, Manoj ;

Gupta, Preeti .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 176 :343-377

[7] Design, Synthesis and Evaluation of a Series of 1,5-Diaryl-1,2,3-triazole-4-carbohydrazones as Inhibitors of the YAP-TAZ/TEAD Complex [J].

Gibault, Floriane ;

Sturbaut, Manon ;

Coevoet, Mathilde ;

Pugniere, Martine ;

Burtscher, Ashley ;

Allemand, Frederic ;

Melnyk, Patricia ;

Hong, Wanjin ;

Rubin, Brian P. ;

Pobbati, Ajaybabu V. ;

Guichou, Jean-Francois ;

Cotelle, Philippe ;

Bailly, Fabrice .

CHEMMEDCHEM, 2021, 16 (18) :2823-2844

[8] 4-Hydroxy-3-methylbenzofuran-2-carbohydrazones as novel LSD1 inhibitors [J].

He, Xingrui ;

Gao, Yuan ;

Hui, Zi ;

Shen, Guodong ;

Wang, Shuo ;

Xie, Tian ;

Ye, Xiang-Yang .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2020, 30 (10)

[9] A semiempirical free energy force field with charge-based desolvation [J].

Huey, Ruth ;

Morris, Garrett M. ;

Olson, Arthur J. ;

Goodsell, David S. .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 2007, 28 (06) :1145-1152

[10] New prospects for the development of selective inhibitors of α-glucosidase based on coumarin-iminothiazolidinone hybrids: Synthesis, in-vitro biological screening and molecular docking analysis [J].

Ibrar, Aliya ;

Zaib, Sumera ;

Khan, Imtiaz ;

Shafique, Zainab ;

Saeed, Aamer ;

Iqbal, Jamshed .

JOURNAL OF THE TAIWAN INSTITUTE OF CHEMICAL ENGINEERS, 2017, 81 :119-133

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