Tehran University of Medical Sciences

Science Communicator Platform

Share By
Potent and Selective Α-Glucosidase Inhibition by Coumarin–Triazole Conjugates: Design, in Vivo Evaluation, and Computational Insights Publisher



Sadeghi Moghadam M ; Bayati B ; Peytam F ; Norouzbahari M ; Gulcan H O ; Mojtabavi S ; Ghasemi F ; Sadat Ebrahimi S E ; Barazandeh Tehrani M ; Sheibani V ; Firoozpour L ; Foroumadi A
Authors

Source: RSC Advances Published:2026


Abstract

Diabetes mellitus is a worldwide health problem, and high blood sugar is one of its hallmarks. Although α-glucosidase inhibitors such as acarbose are crucial for controlling postprandial blood glucose levels, their use is usually limited by digestive adverse effects. As a part of extensive efforts to identify potential anti-diabetic agents, a series of coumarin–triazole conjugates was designed and synthesized. They were evaluated for through in vitro inhibitory assays against α-glucosidase, achieving IC50 values ranging from 1.0 to 223 µM, significantly superior to that of acarbose (IC50 = 750 µM). Among them, compound 12q (bearing 3-CN) emerged as the most potent derivative (IC50 = 1.0 µM) and demonstrated selective inhibition of α-glucosidase over α-amylase. Kinetic studies confirmed 12q as a competitive inhibitor (Ki = 1000 nM), which allowed for its in silico evaluation in the active site. Molecular docking and dynamics simulations revealed the compounds' stable binding in the active site by interactions with critical catalytic residues such as Glu276 and Asp214. Fluorescence and circular dichroism studies supported high-affinity binding without major conformational changes in α-glucosidase. In vivo evaluation in a diabetic mouse model confirmed the significant antihyperglycemic efficacy of compound 12q, which outperformed acarbose in reducing fasting blood glucose and improving glucose tolerance. Collectively, these findings highlight this series of coumarin–triazole hybrids, particularly compound 12q, as promising candidates for the further structural development of safe and potent α-glucosidase inhibitors for diabetes management. This journal is © The Royal Society of Chemistry, 2026.
Related Docs
View other Related Docs
1. 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)
2. Design, Synthesis, and Evaluation of Novel Substituted Imidazo[1,2-C]Quinazoline Derivatives As Potential Α-Glucosidase Inhibitors With Bioactivity and Molecular Docking Insights, Scientific Reports (2024)
3. Design, Synthesis, and Evaluation of Triazolo[1,5-A]Pyridines As Novel and Potent Α‑Glucosidase Inhibitors, Scientific Reports (2025)
Experts (# of related papers)
View all Related Experts
Mohammad Ali Faramarzi (11)
Alireza Foroumadi (10)
Other Related Docs
4. Design, Synthesis, Molecular Docking, and in Vitro Α-Glucosidase Inhibitory Activities of Novel 3-Amino-2,4-Diarylbenzo[4,5]Imidazo[1,2-A]Pyrimidines Against Yeast and Rat Α-Glucosidase, Scientific Reports (2021)
5. A Review on Synthesis, Mechanism of Action, and Structure-Activity Relationships of 1,2,3-Triazole-Based Α-Glucosidase Inhibitors As Promising Anti-Diabetic Agents, Journal of Molecular Structure (2022)
6. Design, Synthesis and Α-Glucosidase Inhibition Study of Novel Pyridazin-Based Derivatives, Medicinal Chemistry Research (2023)
7. Synthesis, In-Vitro Evaluation, Molecular Docking, and Kinetic Studies of Pyridazine-Triazole Hybrid System As Novel Α-Glucosidase Inhibitors, Bioorganic Chemistry (2021)
8. Synthesis, Molecular Docking, and Biological Evaluation of Pyridin-3-Yl-Pyrimidin-2-Yl-Triazole Derivatives As Anti-Cancer Agents, Polycyclic Aromatic Compounds (2024)
9. Synthesis, Molecular Dynamic, and in Silico Study of New Ethyl 4-Arylpyrimido[1,2-B]Indazole-2-Carboxylate: Potential Inhibitors of Α-Glucosidase, Journal of Molecular Structure (2022)
10. Phenyldiazenyl-Phenoxy-1,2,3-Triazol-Acetamide Derivatives As New Dual Cholinesterase Inhibitors: Design, Synthesis, in Vitro, and in Silico Enzymatic Inhibition Evaluations, Journal of Molecular Structure (2025)
11. Rational Design of 3,4,5-Trimethoxyphenyl-Phenoxy-Triazole Derivatives As Highly Potent Α-Glucosidase Inhibitors, European Journal of Medicinal Chemistry Reports (2026)
12. Design and Synthesis of Novel Pyridazine N-Aryl Acetamides: In-Vitro Evaluation of Α-Glucosidase Inhibition, Docking, and Kinetic Studies, Bioorganic Chemistry (2020)
13. Drug Design Strategies for the Treatment Azole-Resistant Candidiasis, Expert Opinion on Drug Discovery (2022)
14. 2,4-Dioxochroman Moiety Linked to 1,2,3-Triazole Derivatives As Novel Α-Glucosidase Inhibitors: Synthesis, in Vitro Biological Evaluation, and Docking Study, Current Organic Chemistry (2020)
15. Design and Synthesis of Novel Quinazolinone-1,2,3-Triazole Hybrids As New Anti-Diabetic Agents: In Vitro Α-Glucosidase Inhibition, Kinetic, and Docking Study, Bioorganic Chemistry (2019)
16. Synthesis, Α-Glucosidase Inhibitory Activity and Docking Studies of Novel Ethyl 1,2,3-Triazol-4-Ylmethylthio-5,6-Diphenylpyridazine-4-Carboxylate Derivatives, BMC Chemistry (2023)
17. Design, Synthesis and Biological Evaluation of Novel Phthalimide-Schiff Base-Coumarin Hybrids As Potent Α-Glucosidase Inhibitors, Chemical Papers (2020)