Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia Publisher Pubmed



Ghasemi M1 ; Mahdavi M2 ; Dehghan M3 ; Eftekharian M4 ; Mojtabavi S5 ; Faramarzi MA5 ; Iraji A6, 7 ; Alharrasi A1
Authors

Source: Scientific Reports Published:2025


Abstract

Diabetes mellitus, particularly type 2 diabetes, is a growing global health challenge characterized by chronic hyperglycemia due to insulin resistance. One therapeutic approach to managing this condition is the inhibition of α-glucosidase, an enzyme involved in carbohydrate digestion, to reduce postprandial blood glucose levels. In this study, a series of thiosemicarbazide-linked quinoline-piperazine derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity, to identify new agents for type 2 diabetes management. Structure-activity relationship (SAR) analysis revealed that the nature and position of substituents on the aryl ring significantly impacted the inhibitory potency. Among the synthesized derivatives, the 2,5-dimethoxy phenyl substitution (7j) exhibited the most potent activity with an IC50 value of 50.0 µM, demonstrating a 15-fold improvement compared to the standard drug acarbose. Kinetic studies identified compound 7j as a competitive inhibitor, with a Ki value of 32 µM. Molecular docking simulations demonstrated key interactions between compound 7j and the active site of α-glucosidase, while molecular dynamics simulations confirmed the stability of the enzyme-ligand complex, reflected in low RMSD and RMSF values. © The Author(s) 2024.
Related Docs
View other Related Docs
1. Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies, Journal of Molecular Structure (2025)
2. Hybrid-Based Design and Biological Evaluation of Quinoline-Benzoylhydrazine Based Derivatives As Α-Glucosidase Inhibitors, Medicinal Chemistry Research (2025)
3. Evaluation of Novel 2-(Quinoline-2-Ylthio)Acetamide Derivatives Linked to Diphenyl-Imidazole As Α-Glucosidase Inhibitors: Insights From in Silico, in Vitro, and in Vivo Studies on Their Anti-Diabetic Properties, European Journal of Medicinal Chemistry (2024)
Experts (# of related papers)
View all Related Experts
Mohammad Ali Faramarzi (20)
Somayeh Mojtabavi (17)
Other Related Docs
4. Synthesis and Structure–Activity Relationship Studies of Benzimidazole-Thioquinoline Derivatives As Α-Glucosidase Inhibitors, Scientific Reports (2023)
5. Synthesis, in Vitro Evaluation, and Molecular Docking Studies of Novel Hydrazineylideneindolinone Linked to Phenoxymethyl-1,2,3-Triazole Derivatives As Potential Α-Glucosidase Inhibitors, Bioorganic Chemistry (2021)
6. Rational Design of New Quinoline-Benzimidazole Scaffold Bearing Piperazine Acetamide Derivatives As Antidiabetic Agents, Bioorganic Chemistry (2024)
7. Design and Synthesis of Novel Quinoline-Piperazines Fused to a Phenylhydrazinecarbothioamide Scaffold As Promising Α-Glucosidase Inhibitors With Anti-Diabetic Potential, Future Medicinal Chemistry (2025)
8. Design, Synthesis, and in Silico Studies of Quinoline-Based-Benzo[D]Imidazole Bearing Different Acetamide Derivatives As Potent Α-Glucosidase Inhibitors, Scientific Reports (2022)
9. Alpha-Glucosidase Inhibitory and Hypoglycemic Effects of Imidazole-Bearing Thioquinoline Derivatives With Different Substituents: In Silico, in Vitro, and in Vivo Evaluations, Bioorganic Chemistry (2024)
10. Quinoline-Thiosemicarbazone-1,2,3-Triazole-Acetamide Derivatives As New Potent Α-Glucosidase Inhibitors, Scientific Reports (2024)
11. Design, Synthesis, and Investigation of Novel 5-Arylpyrazole-Glucose Hybrids As Α-Glucosidase Inhibitors, Scientific Reports (2025)
12. Synthesis, Bioactivity, and Molecular Docking of Benzimidazole-2-Carbamate Derivatives As Potent Α-Glucosidase Inhibitors, Journal of Molecular Structure (2023)
13. Quinazolinone-1,2,3-Triazole-Acetamide Conjugates As Potent Α-Glucosidase Inhibitors: Synthesis, Enzyme Inhibition, Kinetic Analysis, and Molecular Docking Study, RSC Medicinal Chemistry (2023)
14. Aryl-Quinoline-4-Carbonyl Hydrazone Bearing Different 2-Methoxyphenoxyacetamides As Potent Α-Glucosidase Inhibitors; Molecular Dynamics, Kinetic and Structure–Activity Relationship Studies, Scientific Reports (2024)
15. Imidazo[1,2-C]Quinazolines As a Novel and Potent Scaffold of Α-Glucosidase Inhibitors: Design, Synthesis, Biological Evaluations, and in Silico Studies, Scientific Reports (2023)
16. Pyrano[3,2-C]Quinoline Derivatives As New Class of Α-Glucosidase Inhibitors to Treat Type 2 Diabetes: Synthesis, in Vitro Biological Evaluation and Kinetic Study, Medicinal Chemistry (2019)
17. Novel N′-Substituted Benzylidene Benzohydrazides Linked to 1,2,3-Triazoles: Potent Α-Glucosidase Inhibitors, Scientific Reports (2023)
18. New Phenylthiosemicarbazide-Phenoxy-1,2,3-Triazole-N-Phenylacetamides As Dual Inhibitors Against Α-Glucosidase and Ptp-1B for the Treatment of Type 2 Diabetes, Archiv der Pharmazie (2024)
19. Design, Synthesis, and Molecular Docking Studies of Diphenylquinoxaline-6-Carbohydrazide Hybrids As Potent Α-Glucosidase Inhibitors, BMC Chemistry (2022)
20. Design, Synthesis, in Vitro, and in Silico Studies of Novel Diarylimidazole-1,2,3-Triazole Hybrids As Potent Α-Glucosidase Inhibitors, Bioorganic and Medicinal Chemistry (2019)