Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Design, Synthesis, and in Silico Studies of Benzimidazole Bearing Phenoxyacetamide Derivatives As Α-Glucosidase and Α-Amylase Inhibitors Publisher



Shayegan N1 ; Iraji A2, 3 ; Bakhshi N7 ; Moazzam A1 ; Faramarzi MA4 ; Mojtabavi S4 ; Pour SMM5 ; Tehrani MB8 ; Larijani B1 ; Rezaei Z1 ; Yousefi P7 ; Khoshneviszadeh M6, 7 ; Mahdavi M1
Authors

Source: Journal of Molecular Structure Published:2022


Abstract

Benzimidazole bearing phenoxyacetamide derivatives 7a-l were designed and synthesized as anti-diabetic agents. All derivatives were evaluated for in vitro α-glucosidase and α-amylase inhibition. Compounds 7a-l exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 99.6 ± 3.1 - >750 µM compared with standard acarbose (IC50 = 750.0 ± 5.6 µM). Structure-activity relationships showed the important role of methoxy substituent on phenoxy linker to improve the potency. Also, the substitution of 4-F (7j) and 4-Cl (7k) moiety at the Y position improved the inhibitory activity. Enzyme kinetic studies of compound 7j proved that their inhibition was the competitive type with a Ki value of 67.0 µM. The results of α-amylase inhibitory activities indicated that most of the synthesized derivatives had moderate to weak inhibitory activities against α-amylase. Among them, compounds 7c (X = H; Y = 2-Br) and 7j (X = OMe; Y = 4-F) showed the strongest inhibition with 50.0% and 45.0% inhibition at 108 µM. Molecular docking studies were performed to understand the binding interaction of the compounds. © 2022 Elsevier B.V.
Related Docs
View other Related Docs
1. Design, Synthesis, and in Silico Studies of Quinoline-Based-Benzo[D]Imidazole Bearing Different Acetamide Derivatives As Potent Α-Glucosidase Inhibitors, Scientific Reports (2022)
2. Synthesis and Structure–Activity Relationship Studies of Benzimidazole-Thioquinoline Derivatives As Α-Glucosidase Inhibitors, Scientific Reports (2023)
3. 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)
Experts (# of related papers)
View all Related Experts
Mohammad Ali Faramarzi (20)
Somayeh Mojtabavi (16)
Other Related Docs
4. Design, Synthesis, and Molecular Docking Studies of Diphenylquinoxaline-6-Carbohydrazide Hybrids As Potent Α-Glucosidase Inhibitors, BMC Chemistry (2022)
5. Synthesis and Bioactivities Evaluation of Quinazolin-4(3H)-One Derivatives As Α-Glucosidase Inhibitors, BMC Chemistry (2022)
6. Cyanoacetohydrazide Linked to 1,2,3-Triazole Derivatives: A New Class of Α-Glucosidase Inhibitors, Scientific Reports (2022)
7. Novel N′-Substituted Benzylidene Benzohydrazides Linked to 1,2,3-Triazoles: Potent Α-Glucosidase Inhibitors, Scientific Reports (2023)
8. Synthesis, in Vitro Α-Glucosidase Inhibitory Activities, and Molecular Dynamic Simulations of Novel 4-Hydroxyquinolinone-Hydrazones As Potential Antidiabetic Agents, Scientific Reports (2023)
9. 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)
10. Α-Glucosidase and Α-Amylase Inhibition, Molecular Modeling and Pharmacokinetic Studies of New Quinazolinone-1,2,3-Triazole-Acetamide Derivatives, Medicinal Chemistry Research (2021)
11. 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)
12. 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)
13. 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)
14. 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)
15. 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)
16. Synthesis and Biological Evaluation of New Benzimidazole-1,2,3-Triazole Hybrids As Potential Α-Glucosidase Inhibitors, Bioorganic Chemistry (2020)
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. Design and Synthesis of Phenoxymethybenzoimidazole Incorporating Different Aryl Thiazole-Triazole Acetamide Derivatives As Α-Glycosidase Inhibitors, Molecular Diversity (2022)
19. 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)
20. Indole-Carbohydrazide Linked Phenoxy-1,2,3-Triazole-N-Phenylacetamide Derivatives As Potent Α-Glucosidase Inhibitors: Design, Synthesis, in Vitro Α-Glucosidase Inhibition, and Computational Studies, BMC Chemistry (2023)