Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies

Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies Publisher

Ghasemi M¹ ; Iraji A^{2, 3} ; Dehghan M⁴ ; Nosood YL¹ ; Ghanavieh NF¹ ; Hashempur MH³ ; Mojtabavi S⁵ ; Faramarzi MA⁵ ; Mahdavi M⁶ ; 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. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3. Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
4. School of Chemistry, College of Science, University of Tehran, Tehran, 14155-6455, Iran
5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Molecular Structure Published:2025

Abstract

α-Glucosidase inhibitors are crucial therapeutic agents for managing postprandial hyperglycemia in type 2 diabetes mellitus (T2DM). This study focuses on designing, synthesizing, and evaluating a new series of quinoline-piperazine-acetamide derivatives as potential α-glucosidase inhibitors. These derivatives introduce a unique combination of a quinoline core with a flexible piperazine linker, as new scaffold for α-glucosidase inhibition. This structural modification is hypothesized to enhance enzyme interaction. The synthesized derivatives were tested in vitro for their inhibitory activity, with compound 6m (benzyl) showing significant inhibition, with IC50 values of 280.0 µM compared to the standard drug acarbose (IC50 = 750.7 µM). Molecular docking studies revealed crucial pi-pi stacking and pi-cation interactions with key residues such as His239 and Phe231, along with hydrogen bonding with Lys155, Pro309, and Thr215, which enhanced the inhibitory potency of the active compounds. Furthermore, molecular dynamics simulations confirmed that 6m consistently maintained stability within the active site of α-glucosidase throughout the simulation. These findings suggest that the synthesized compounds hold promise as α-glucosidase inhibitors for adjusting blood sugar control and metabolic health. © 2024

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Mohammad Mahdavi (4)

Mohammad Ali Faramarzi (3)

Style	Citing Format
MLA	Ghasemi M, et al.. "Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies." Journal of Molecular Structure, vol. 1323, no. , 2025, pp. -.
APA	Ghasemi M, Iraji A, Dehghan M, Nosood YL, Ghanavieh NF, Hashempur MH, Mojtabavi S, Faramarzi MA, Mahdavi M, Alharrasi A (2025). Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies. Journal of Molecular Structure, 1323(), -.
Chicago	Ghasemi M, Iraji A, Dehghan M, Nosood YL, Ghanavieh NF, Hashempur MH, Mojtabavi S, Faramarzi MA, Mahdavi M, Alharrasi A. "Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies." Journal of Molecular Structure 1323, no. (2025): -.
Harvard	Ghasemi M et al. (2025) 'Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies', Journal of Molecular Structure, 1323(), pp. -.
Vancouver	Ghasemi M, Iraji A, Dehghan M, Nosood YL, Ghanavieh NF, Hashempur MH, et al.. Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies. Journal of Molecular Structure. 2025;1323():-.
BibTex	@article{ author = {Ghasemi M and Iraji A and Dehghan M and Nosood YL and Ghanavieh NF and Hashempur MH and Mojtabavi S and Faramarzi MA and Mahdavi M and Alharrasi A}, title = {Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies}, journal = {Journal of Molecular Structure}, volume = {1323}, number = {}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Ghasemi M AU - Iraji A AU - Dehghan M AU - Nosood YL AU - Ghanavieh NF AU - Hashempur MH AU - Mojtabavi S AU - Faramarzi MA AU - Mahdavi M AU - Alharrasi A TI - Quinoline-Piperazine Derivatives As Potential Α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, and in Silico Studies JO - Journal of Molecular Structure VL - 1323 IS - SP - EP - PY - 2025 ER -

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