Isfahan University of Medical Sciences

Science Communicator Platform

Share By
Drug Repurposing for Diabetes Mellitus: In Silico and in Vitro Investigation of Drugbank Database for Α-Glucosidase Inhibitors Publisher Pubmed

Summary: Scientists found Forodesine may treat diabetes by inhibiting α-glucosidase, showing promise as a new therapy option. #Diabetes #DrugDiscovery

Sadeghi M1 ; Miroliaei M1 ; Ghanadian M2
Authors

Source: International Journal of Biological Macromolecules Published:2024


Abstract

The process of developing novel compounds/drugs is arduous, time-intensive, and financially burdensome, characterized by a notably low success rate and relatively high attrition rates. To alleviate these challenges, compound/drug repositioning strategies are employed to predict potential therapeutic effects for DrugBank-approved compounds across various diseases. In this study, we devised a computational and enzyme inhibitory mechanistic approach to identify promising compounds from the pool of DrugBank-approved substances targeting Diabetes Mellitus (DM). Molecular docking analyses were employed to validate the binding interaction patterns and conformations of the screened compounds within the active site of α-glucosidase. Notably, Asp352 and Glu277 participated in interactions within the α-glucosidase-ligand complexes, mediated by conventional hydrogen bonding and van der Waals forces, respectively. The stability of the docked complexes (α-glucosidase-compounds) was scrutinized through Molecular Dynamics (MD) simulations. Subsequent in vitro analyses assessed the therapeutic potential of the repositioned compounds against α-glucosidase. Kinetic studies revealed that “Forodesine” exhibited a lower IC50 (0.24 ± 0.04 mM) compared to the control, and its inhibitory pattern corresponds to that of competitive inhibitors. In-depth in silico secondary structure content analysis detailed the interactions between Forodesine and α-glucosidase, unveiling significant alterations in enzyme conformation upon binding, impacting its catalytic activity. Overall, our findings underscore the potential of Forodesine as a promising candidate for DM treatment through α-glucosidase inhibition. Further validation through in vitro and in vivo studies is imperative to confirm the therapeutic benefits of Forodesine in conformational diseases such as DM. © 2024 Elsevier B.V.
Related Docs
View other Related Docs
1. Exploring the Inhibitory Properties of Biflavonoids on Α-Glucosidase; Computational and Experimental Approaches, International Journal of Biological Macromolecules (2023)
2. Inhibitory Effect of Flavonoid Glycosides on Digestive Enzymes: In Silico, in Vitro, and in Vivo Studies, International Journal of Biological Macromolecules (2022)
3. The Inhibitory Potential of Natural Compounds on Α-Amylase and Α-Glucosidase in the Management of Type 2 Diabetes, Iranian Journal of Chemistry and Chemical Engineering (2024)
Experts (# of related papers)
View all Related Experts
Lotfollah Saghaie Dehkordi (6)
Afshin Fassihi (6)
Drug Repurposing for Diabetes Mellitus: In Silico and in Vitro Investigation of Drugbank Database for Α-Glucosidase Inhibitors
Other Related Docs
4. Identification of Cholinesterases Inhibitors From Flavonoids Derivatives for Possible Treatment of Alzheimer's Disease: In Silico and in Vitro Approaches, Current Research in Structural Biology (2024)
5. Design and Synthesis of Novel Pyrazole-Phenyl Semicarbazone Derivatives As Potential Α-Glucosidase Inhibitor: Kinetics and Molecular Dynamics Simulation Study, International Journal of Biological Macromolecules (2021)
6. The Impact of Ages on Human Health and the Development of Their Inhibitors Based on Natural Compounds, Arabian Journal of Chemistry (2023)
7. Design, Synthesis, and Evaluation of Triazolo[1,5-A]Pyridines As Novel and Potent Α‑Glucosidase Inhibitors, Scientific Reports (2025)
8. Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Pyrazole-Benzofuran Hybrids As New Α-Glucosidase Inhibitor, Scientific Reports (2021)
9. Quantum Processing of Cytidine Derivatives and Evaluating Their in Silico Interactions With the Covid-19 Main Protease, Main Group Chemistry (2022)
10. In Silico Approach for Designing Potent Inhibitors Against Tyrosinase, Biosciences Biotechnology Research Asia (2015)
11. Novel Aldimine-Type Schiff Bases of 4-Amino-5-[(3,4,5-Trimethoxyphenyl)Methyl]-1,2,4-Triazole-3-Thione/Thiol: Docking Study, Synthesis, Biological Evaluation, and Anti-Tubulin Activity, Archiv der Pharmazie (2016)
12. Effect of Biomolecular Conformation on Docking Simulation: A Case Study on a Potent Hiv-1 Protease Inhibitor, Iranian Journal of Pharmaceutical Research (2015)
13. Drug Repurposing Against Angiotensin-Converting Enzyme-Related Carboxypeptidase (Ace2) Through Computational Approach, Journal of Medical Signals and Sensors (2022)
14. Characterization of Adenosine Receptor in Its Native Environment: Insights From Molecular Dynamics Simulations of Palmitoylated/Glycosylated, Membrane-Integrated Human A2b Adenosine Receptor, Journal of Molecular Modeling (2012)
15. Design and Synthesis of Novel Quinazolinone-Pyrazole Derivatives As Potential Α-Glucosidase Inhibitors: Structure-Activity Relationship, Molecular Modeling and Kinetic Study, Bioorganic Chemistry (2021)
16. Synthesis, Molecular Docking and Molecular Dynamics Simulation of 2- Thioxothiazolidin-4-One Derivatives Against Gp41, Current HIV Research (2020)
17. Virtual Screening for the Identification of Potential Candidate Molecules Against Envelope (E) and Membrane (M) Proteins of Sars-Cov-2, Journal of Computational Biophysics and Chemistry (2021)
18. Molecular Modelling Study on Pyrrolo[2,3-B]Pyridine Derivatives As C-Met Kinase Inhibitors: A Combined Approach Using Molecular Docking, 3D-Qsar Modelling and Molecular Dynamics Simulation, Molecular Simulation (2020)
19. Qsar and Docking Studies of Some 1,2,3,4-Tetrahydropyrimidines: Evaluation of Gp41 As Possible Target for Anti-Hiv-1 Activity, Medicinal Chemistry Research (2015)
20. Gp41 Inhibitory Activity Prediction of Theaflavin Derivatives Using Ligand/Structure-Based Virtual Screening Approaches, Computational Biology and Chemistry (2019)