Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
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 Publisher Pubmed

Summary: Can new compounds control diabetes? A study found quinoline-imidazole derivatives strongly inhibit α-glucosidase, reducing blood sugar in rats, promising for diabetes treatment. #DiabetesResearch #DrugDevelopment

Khalili Ghomi M1, 2 ; Noori M2, 3 ; Mirahmad M2 ; Iraji A4, 5 ; Sadr AS6, 7 ; Dastyafteh N2, 3 ; Asili P2 ; Gholami M8 ; Javanshir S3 ; Lotfi M9 ; Mojtabavi S10 ; Faramarzi MA10 ; Asadi M11 ; Nasliesfahani E12 Show All Authors
Authors
  1. Khalili Ghomi M1, 2
  2. Noori M2, 3
  3. Mirahmad M2
  4. Iraji A4, 5
  5. Sadr AS6, 7
  6. Dastyafteh N2, 3
  7. Asili P2
  8. Gholami M8
  9. Javanshir S3
  10. Lotfi M9
  11. Mojtabavi S10
  12. Faramarzi MA10
  13. Asadi M11
  14. Nasliesfahani E12
  15. Palimi M13
  16. Larijani B2
  17. Meshkatalsadat MH1
  18. Mahdavi M2

Source: European Journal of Medicinal Chemistry Published:2024


Abstract

The inhibition of the α-glucosidase enzyme is crucial for targeting type 2 diabetes mellitus (DM). This study introduces a series of synthetic analogs based on thiomethylacetamide-quinoline derivatives linked to diphenyl-imidazole as highly potential α-glucosidase inhibitors. Twenty derivatives were synthesized and screened in vitro against α-glucosidase, revealing IC50 values ranging from 0.18 ± 0.00 to 2.10 ± 0.07 μM, in comparison to the positive control, acarbose. Among these derivatives, compound 10c (IC50 = 0.180 μM) demonstrated the highest potency and revealed a competitive inhibitory mechanism in kinetic studies (Ki = 0.15 μM). Docking and molecular dynamic evaluations elucidated the binding mode of 10c with the active site residues of the α-glucosidase enzyme. Moreover, in vivo assessments on a rat model of DM affirmed the anti-diabetic efficacy of 10c, evidenced by reduced fasting and overall blood glucose levels. The histopathological evaluation enhanced pancreatic islet architecture and hepatocytes in liver sections. In conclusion, novel 2-(quinoline-2-ylthio)acetamide derivatives as potent α-glucosidase inhibitors were developed. Compound 10c emerged as a promising candidate for diabetes management, warranting further investigation for potential clinical applications and mechanistic insights. © 2024
Related Docs
View other Related Docs
1. 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)
2. Design, Synthesis, and in Silico Studies of Quinoline-Based-Benzo[D]Imidazole Bearing Different Acetamide Derivatives As Potent Α-Glucosidase Inhibitors, Scientific Reports (2022)
3. Synthesis, in Vitro Potency of Inhibition, Enzyme Kinetics and in Silico Studies of Quinoline-Based Α-Glucosidase Inhibitors, Scientific Reports (2024)
Experts (# of related papers)
View all Related Experts
Somayeh Mojtabavi (18)
Mohammad Ali Faramarzi (18)
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
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 Inhibitor Screening, Structure–Activity Relationship, and Molecular Dynamic Simulation Studies of Novel Thioquinoline Derivatives As Potent Α-Glucosidase Inhibitors, Scientific Reports (2023)
6. Cyanoacetohydrazide Linked to 1,2,3-Triazole Derivatives: A New Class of Α-Glucosidase Inhibitors, Scientific Reports (2022)
7. Synthesis and Bioactivities Evaluation of Quinazolin-4(3H)-One Derivatives As Α-Glucosidase Inhibitors, BMC Chemistry (2022)
8. Design, Synthesis, and in Silico Studies of Benzimidazole Bearing Phenoxyacetamide Derivatives As Α-Glucosidase and Α-Amylase Inhibitors, Journal of Molecular Structure (2022)
9. 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)
10. Design, Synthesis, and Molecular Docking Studies of Diphenylquinoxaline-6-Carbohydrazide Hybrids As Potent Α-Glucosidase Inhibitors, BMC Chemistry (2022)
11. Novel Pyrano[3,2-C]Quinoline-1,2,3-Triazole Hybrids As Potential Anti-Diabetic Agents: In Vitro Α-Glucosidase Inhibition, Kinetic, and Molecular Dynamics Simulation, ACS Omega (2023)
12. Synthesis, in Vitro Α-Glucosidase Inhibitory Activities, and Molecular Dynamic Simulations of Novel 4-Hydroxyquinolinone-Hydrazones As Potential Antidiabetic Agents, Scientific Reports (2023)
13. Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase, Scientific Reports (2023)
14. 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)
15. Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia, Scientific Reports (2025)
16. Pyrano[2,3-B]Chromone Derivatives As Novel Dual Inhibitors of Α-Glucosidase and Α-Amylase: Design, Synthesis, Biological Evaluation, and in Silico Studies, Bioorganic Chemistry (2024)
17. 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)
18. Quinoline-Thiosemicarbazone-1,2,3-Triazole-Acetamide Derivatives As New Potent Α-Glucosidase Inhibitors, Scientific Reports (2024)
19. In Silico and in Vitro Studies of Thiosemicarbazone-Indole Hybrid Compounds As Potent Α-Glycosidase Inhibitors, Computational Biology and Chemistry (2022)
20. New Solid Phase Methodology for the Synthesis of Biscoumarin Derivatives: Experimental and in Silico Approaches, BMC Chemistry (2022)