Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) 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



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
Show Affiliations
Authors Affiliations
  1. 1. Department of Chemistry, Qom University of Technology, Qom, Iran
  2. 2. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Pharmaceutical and Heterocyclic Chemistry Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran, 16846-13114, Iran
  4. 4. Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  6. 6. Computer Science Department, Mathematical Sciences Faculty, Shahid Beheshti University, Tehran, Iran
  7. 7. School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran
  8. 8. Toxicology and Diseases Specialty Group, Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Pathology, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Science, Tehran, Iran
  12. 12. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  13. 13. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

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. 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)
3. Synthesis, in Vitro Potency of Inhibition, Enzyme Kinetics and in Silico Studies of Quinoline-Based Α-Glucosidase Inhibitors, Scientific Reports (2024)
4. Synthesis and Structure–Activity Relationship Studies of Benzimidazole-Thioquinoline Derivatives As Α-Glucosidase Inhibitors, Scientific Reports (2023)
5. Design, Synthesis, and in Silico Studies of Quinoline-Based-Benzo[D]Imidazole Bearing Different Acetamide Derivatives As Potent Α-Glucosidase Inhibitors, Scientific Reports (2022)
6. Cyanoacetohydrazide Linked to 1,2,3-Triazole Derivatives: A New Class of Α-Glucosidase Inhibitors, Scientific Reports (2022)
7. Design, Synthesis, and in Silico Studies of Benzimidazole Bearing Phenoxyacetamide Derivatives As Α-Glucosidase and Α-Amylase Inhibitors, Journal of Molecular Structure (2022)
8. Design and Synthesis of Novel Nitrothiazolacetamide Conjugated to Different Thioquinazolinone Derivatives As Anti-Urease Agents, Scientific Reports (2022)
Experts (# of related papers)
View all Related Experts
Mohammad Mahdavi (42)
Mohammad Ali Faramarzi (37)
Other Related Docs
9. Synthesis, in Vitro Α-Glucosidase Inhibitory Activities, and Molecular Dynamic Simulations of Novel 4-Hydroxyquinolinone-Hydrazones As Potential Antidiabetic Agents, Scientific Reports (2023)
10. Synthesis and Bioactivities Evaluation of Quinazolin-4(3H)-One Derivatives As 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. Design, Synthesis, and Molecular Docking Studies of Diphenylquinoxaline-6-Carbohydrazide Hybrids As Potent Α-Glucosidase Inhibitors, BMC Chemistry (2022)
13. New Solid Phase Methodology for the Synthesis of Biscoumarin Derivatives: Experimental and in Silico Approaches, BMC Chemistry (2022)
14. Quinoline-Thiosemicarbazone-1,2,3-Triazole-Acetamide Derivatives As New Potent Α-Glucosidase Inhibitors, Scientific Reports (2024)
15. New Thioxothiazolidinyl-Acetamides Derivatives As Potent Urease Inhibitors: Design, Synthesis, in Vitro Inhibition, and Molecular Dynamic Simulation, Scientific Reports (2023)
16. In Silico and in Vitro Studies of Thiosemicarbazone-Indole Hybrid Compounds As Potent Α-Glycosidase Inhibitors, Computational Biology and Chemistry (2022)
17. 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)
18. Discovery of Novel 4,5-Diphenyl-Imidazol-Α-Aminophosphonate Hybrids As Promising Anti-Diabetic Agents: Design, Synthesis, in Vitro, and in Silico Enzymatic Studies, Bioorganic Chemistry (2023)
19. [1,2,4]Triazolo[3,4-B][1,3,4]Thiadiazole Derivatives As New Therapeutic Candidates Against Urease Positive Microorganisms: Design, Synthesis, Pharmacological Evaluations, and in Silico Studies, Scientific Reports (2023)
20. 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)
21. 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)
22. 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)
23. Synthesis and Biological Evaluation of 2-(2-Methyl-1H-Pyrrol-3-Yl)-2-Oxo-N-(Pyridine-3-Yl) Acetamide Derivatives: In Vitro Α-Glucosidase Inhibition, and Kinetic and Molecular Docking Study, Chemical Papers (2020)
24. New Engineered Fusion Peptide With Dual Functionality: Antibacterial and Strong Binding to Hydroxyapatite, International Journal of Peptide Research and Therapeutics (2020)
25. 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)
26. Novel N′-Substituted Benzylidene Benzohydrazides Linked to 1,2,3-Triazoles: Potent Α-Glucosidase Inhibitors, Scientific Reports (2023)
27. Design, Synthesis Docking and Molecular Dynamics Studies of 2-Amino-4-Phenylthiazole-Indole Hybrids As Α-Glucosidase Inhibitors, Journal of Molecular Structure (2024)
28. Novel Coumarin Containing Dithiocarbamate Derivatives As Potent Α-Glucosidase Inhibitors for Management of Type 2 Diabetes, Medicinal Chemistry (2021)
29. Exome Sequencing Reveals Novel Rare Variants in Iranian Familial Multiple Sclerosis: The Importance of Pold2 in the Disease Pathogenesis, Genomics (2021)
30. Thioquinoline Derivatives Conjugated to Thiosemicarbazide As Potent Tyrosinase Inhibitors With Anti-Melanogenesis Properties, Scientific Reports (2023)
31. Unveiling the Structure of Gpi-Anchored Protein of Malassezia Globosa and Its Pathogenic Role in Pityriasis Versicolor, Journal of Molecular Modeling (2021)
32. Substituted Piperazine Conjugated to Quinoline-Thiosemicarbazide As Potent Α-Glucosidase Inhibitors to Target Hyperglycemia, Scientific Reports (2025)
33. Design and Synthesis of New Imidazo[1,2-B]Pyrazole Derivatives, in Vitro Α-Glucosidase Inhibition, Kinetic and Docking Studies, Molecular Diversity (2020)
34. 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)
35. Hybrid-Based Design and Biological Evaluation of Quinoline-Benzoylhydrazine Based Derivatives As Α-Glucosidase Inhibitors, Medicinal Chemistry Research (2025)
36. 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)
37. New Acridine-9-Carboxamide Linked to 1,2,3-Triazole-N-Phenylacetamide Derivatives As Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro, and in Silico Biological Evaluations, Medicinal Chemistry Research (2020)
38. Investigation of Specific Binding of Designed Oligodeoxynucleotide Decoys to Transcription Factors in Ht29 Cell Line Undergoing Epithelial–Mesenchymal Transition (Emt), Journal of Cellular Physiology (2019)
39. 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)
40. Synthesis and Biological Evaluation of New Benzimidazole-1,2,3-Triazole Hybrids As Potential Α-Glucosidase Inhibitors, Bioorganic Chemistry (2020)
41. Identification of New Dna Gyrase Inhibitors Based on Bioactive Compounds From Streptomyces: Structure-Based Virtual Screening and Molecular Dynamics Simulations Approaches, Journal of Biomolecular Structure and Dynamics (2020)
42. Synthesis and Biological Evaluation of New Dihydroindolizino[8,7-B]Indole Derivatives As Novel Α-Glucosidase Inhibitors, Journal of Molecular Structure (2021)
43. Design and Synthesis of Novel Quinazolinone-Pyrazole Derivatives As Potential Α-Glucosidase Inhibitors: Structure-Activity Relationship, Molecular Modeling and Kinetic Study, Bioorganic Chemistry (2021)
44. Synthesis, in Vitro and in Silico Enzymatic Inhibition Assays, and Toxicity Evaluations of New 4,5-Diphenylimidazole-N-Phenylacetamide Derivatives As Potent Α-Glucosidase Inhibitors, Medicinal Chemistry Research (2021)
45. Design and Synthesis of 4,5-Diphenyl-Imidazol-1,2,3-Triazole Hybrids As New Anti-Diabetic Agents: In Vitro Α-Glucosidase Inhibition, Kinetic and Docking Studies, Molecular Diversity (2021)
46. Synthesis and in Vitro Urease Inhibitory Activity of 5-Nitrofuran-2-Yl-Thiadiazole Linked to Different Cyclohexyl-2-(Phenylamino)Acetamides, in Silico and Kinetic Studies, Bioorganic Chemistry (2022)
47. Optimization of Conformational Stability and Catalytic Efficiency in Chondroitinase Abc Ι by Protein Engineering Methods, Engineering in Life Sciences (2016)
48. Arylmethylene Hydrazine Derivatives Containing 1,3-Dimethylbarbituric Moiety As Novel Urease Inhibitors, Scientific Reports (2021)
49. 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)
50. Structure-Based Development of 3,5-Dihydroxybenzoyl-Hydrazineylidene As Tyrosinase Inhibitor; in Vitro And in Silico Study, Scientific Reports (2024)