BIOMAT Database Logo BIOMAT Database Logo

Synthesis, biological evaluation and action mechanism of 7H-[1,2,4] triazolo [3,4-b] [1,3,4] thiadiazine-phenylhydrazone derivatives as α-glucosidase inhibitors. 2023

Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Clinical Trails Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China.

In our work, several 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-phenylhydrazone derivatives as α-glucosidase inhibitors (α-GIs) were synthesized and characterized by 1H NMR, 13C NMR, and HRMS spectrum. Then, their bio-activity against the α-glucosidase (α-Glu) was further evaluated. Among them, almost all compounds displayed better bio-activity with IC50 from 31.23 ± 0.89 to 213.50 ± 4.19 μM than acarbose (IC50 = 700.20 ± 10.55 μM). In particular, compound 5o showed the best potency to inhibit α-Glu in a mixed manner. Moreover, the action mechanisms of 5o were further clarified including fluorescence quenching, circular dichroism spectra, three-dimensional fluorescence spectra, molecular docking, etc. All mechanism studies revealed that 5o could arouse the changed secondary structure of α-Glu to hinder enzyme catalytic activity. It was observed from an in vivo study that 5o of 20 mg/kg could significantly decrease by 24.45 % postprandial blood glucose in mice vs. the control. Meanwhile, 5o had low drug-drug interaction potential and was likely to be an orally active compound. Moreover, 5o was observed to be no obvious cytotoxicity to HEK-293 cells. In summary, compound 5o exhibited one potential to be further applied as an antidiabetic drug.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000520 alpha-Glucosidases Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II. Acid Maltase,Lysosomal alpha-Glucosidase,Maltase,Maltases,Maltase-Glucoamylase,Neutral Maltase,Neutral alpha-Glucosidase,alpha-Glucosidase,Lysosomal alpha Glucosidase,Maltase Glucoamylase,Neutral alpha Glucosidase,alpha Glucosidase,alpha Glucosidases,alpha-Glucosidase, Lysosomal,alpha-Glucosidase, Neutral
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013829 Thiadiazines
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057809 HEK293 Cells A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5. 293T Cells,HEK 293 Cell Line,HEK 293 Cells,Human Embryonic Kidney Cell Line 293,Human Kidney Cell Line 293,293 Cell, HEK,293 Cells, HEK,293T Cell,Cell, 293T,Cell, HEK 293,Cell, HEK293,Cells, 293T,Cells, HEK 293,Cells, HEK293,HEK 293 Cell,HEK293 Cell
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking
D065089 Glycoside Hydrolase Inhibitors Compounds that inhibit or block the activity of GLYCOSIDE HYDROLASES such as ALPHA-AMYLASES and ALPHA-GLUCOSIDASES. alpha-Glucosidase Inhibitor,alpha-Glucosidase Inhibitors,Intestinal alpha-Amylase Inhibitors,Pancreatic alpha-Amylase Inhibitors,alpha-Amylase Inhibitors, Pancreatic,Hydrolase Inhibitors, Glycoside,Inhibitor, alpha-Glucosidase,Inhibitors, Glycoside Hydrolase,Inhibitors, Intestinal alpha-Amylase,Inhibitors, Pancreatic alpha-Amylase,Inhibitors, alpha-Glucosidase,Intestinal alpha Amylase Inhibitors,Pancreatic alpha Amylase Inhibitors,alpha Amylase Inhibitors, Pancreatic,alpha Glucosidase Inhibitor,alpha Glucosidase Inhibitors,alpha-Amylase Inhibitors, Intestinal

Related Publications

Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Design, Synthesis, and Biological Evaluation of Novel 7H-[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazine Inhibitors as Antitumor Agents.
August 2020, ACS omega,
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Carboxymethyl- and carboxy-derivatives of 7H- and 5H-1,2,4-triazolo [3,4-b][1,3,4] thiadiazine: synthesis and biological evaluation.
October 1989, Farmaco (Societa chimica italiana : 1989),
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Synthesis and antimicrobial testing of 4H-1,2,4-triazole, 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives of 1H-benzimidazole.
November 1997, Die Pharmazie,
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity.
November 2022, Molecules (Basel, Switzerland),
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Synthesis, crystal structure and biological evaluation of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines.
May 2014, European journal of medicinal chemistry,
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Synthesis and antimicrobial activity of some novel fused heterocyclic 1,2,4-triazolo [3,4-b][1,3,4] thiadiazine derivatives.
April 2014, Journal of advanced pharmaceutical technology & research,
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
3-(2-furyl)-6-(4-methylphenyl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazine and its 6-phenyl analogue.
February 2000, Acta crystallographica. Section C, Crystal structure communications,
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Synthesis and Anti-Breast Cancer Potency of Mono- and Bis-(pyrazolyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine) Derivatives as EGFR/CDK-2 Target Inhibitors.
September 2023, ACS omega,
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Synthesis, antifungal activity and mechanism of action of novel chalcone derivatives containing 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole.
April 2024, Molecular diversity,
Qianqian Feng, and Jinfeng Zhang, and Shuang Luo, and Yong Huang, and Zhiyun Peng, and Guangcheng Wang
Design, synthesis and structure-activity relationship of 3,6-diaryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines as novel tubulin inhibitors.
September 2017, Scientific reports,
Copied contents to your clipboard!