Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia

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 A^{6, 7} ; Alharrasi A¹

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1. Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box 33, Birkat Al Mauz, Nizwa, Oman
2. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
3. School of Chemistry, College of Science, University of Tehran, Tehran, 14155-6455, Iran
4. Student Research Committee, Jahrom Univesity of Medical Sciences, Jahrom, Iran
5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
6. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
7. Department of Persian Medicine, School of Medicine, Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

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.

2. Synthesis and Structure–Activity Relationship Studies of Benzimidazole-Thioquinoline Derivatives As Α-Glucosidase Inhibitors, Scientific Reports (2023)

3. 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)

4. 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)

5. 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)

6. Quinoline-Thiosemicarbazone-1,2,3-Triazole-Acetamide Derivatives As New Potent Α-Glucosidase Inhibitors, Scientific Reports (2024)

7. Design, Synthesis, and in Silico Studies of Quinoline-Based-Benzo[D]Imidazole Bearing Different Acetamide Derivatives As Potent Α-Glucosidase Inhibitors, Scientific Reports (2022)

8. Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies, Journal of Molecular Structure (2025)

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Somayeh Mojtabavi (8)

Mohammad Ali Faramarzi (8)

Style	Citing Format
MLA	Ghasemi M, et al.. "Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia." Scientific Reports, vol. 15, no. 1, 2025, pp. -.
APA	Ghasemi M, Mahdavi M, Dehghan M, Eftekharian M, Mojtabavi S, Faramarzi MA, Iraji A, Alharrasi A (2025). Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia. Scientific Reports, 15(1), -.
Chicago	Ghasemi M, Mahdavi M, Dehghan M, Eftekharian M, Mojtabavi S, Faramarzi MA, Iraji A, Alharrasi A. "Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia." Scientific Reports 15, no. 1 (2025): -.
Harvard	Ghasemi M et al. (2025) 'Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia', Scientific Reports, 15(1), pp. -.
Vancouver	Ghasemi M, Mahdavi M, Dehghan M, Eftekharian M, Mojtabavi S, Faramarzi MA, et al.. Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia. Scientific Reports. 2025;15(1):-.
BibTex	@article{ author = {Ghasemi M and Mahdavi M and Dehghan M and Eftekharian M and Mojtabavi S and Faramarzi MA and Iraji A and Alharrasi A}, title = {Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia}, journal = {Scientific Reports}, volume = {15}, number = {1}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Ghasemi M AU - Mahdavi M AU - Dehghan M AU - Eftekharian M AU - Mojtabavi S AU - Faramarzi MA AU - Iraji A AU - Alharrasi A TI - Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia JO - Scientific Reports VL - 15 IS - 1 SP - EP - PY - 2025 ER -

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